Management Of Epilepsy Research Articles

Study on Factors Associated with Poor Seizure Control in Epileptic Patients during Pregnancy

The management of epilepsy during pregnancy is always challenging. This study aims to analyze the factors associated with poor seizure control during pregnancy and to describe the most commonly used antiseizure drugs in these patients. We conducted a casecontrol study of pregnant patients with epilepsy between 2017 and 2022. 50 pregnant women with poorly controlled epilepsy were taken as cases and 50 pregnant women with well-controlled epilepsy were taken as controls. Patients were evaluated in the first and second trimesters of pregnancy and after delivery. Patients’ mean age was 32.6 years. 53% had focal epilepsy, 40% had generalized epilepsy and 5 % had undetermined epilepsy. The factors associated with poor control of seizure during pregnancy were duration of epilepsy, poor seizure control in the year prior to pregnancy, treatment with 2 or more antiseizure drugs, untreated epilepsy, missed medication dosages, decline in plasma concentrations of antiepileptic drug, presence of focal activity in EEG and abnormal imaging findings. Anti-seizure medications most widely used in monotherapy were lamotrigine, levetiracetam, carbamazepine, and valproate. EWMCJ Vol. 12, No. 1&2, January-July 2024: 99-103

Metabolic Reprogramming via Ketogenic Diet: A Novel Approach to Combating Neurological Diseases

Epilepsy is a chronic neurological disorder characterized by a persistent tendency for the brain to generate seizures, affecting approximately 0.5–1% of the global population. Despite advances in pharmacological treatments and surgical interventions, around 30% of individuals with epilepsy continue to experience seizures, leading to significant impacts on quality of life. Among these individuals, many suffer from drug-resistant epilepsy (DRE), where seizures persist despite optimal drug therapy or surgical interventions.In recent years, the ketogenic diet (KD)—a high-fat, low-carbohydrate dietary regimen—has emerged as an effective non-pharmacological strategy for managing DRE. The KD works by inducing ketosis, a metabolic state where the body uses fat as the primary energy source instead of carbohydrates, which has been associated with neuroprotective effects and significant seizure reduction. Variants of the KD, such as the Modified Atkins Diet (MAD) and Low Glycemic Index Treatment (LGIT), offer less restrictive alternatives that have shown similar efficacy in reducing seizure frequency.This review explores the cellular and molecular mechanisms of the KD, evaluates its safety and tolerability across different age groups, and assesses its efficacy in treating epilepsy, particularly DRE. The findings underscore the potential of personalized dietary interventions to serve as effective adjunctive therapies in the management of epilepsy, offering new hope for individuals who do not respond to conventional treatments.

Nano-formulations for the Management of Epilepsy: Synthetic and Herbal Drug Perspectives

Introduction: Epilepsy is a multifaceted neurological disorder impacting many individuals globally. Although the main treatment method is through medicines, many patients do not respond to existing drugs. This has spurred extensive research for new therapeutic targets and drug delivery methods. Inflammation and oxidative stress have been associated with the development and progression of epilepsy. Nanomedicine-based treatments focussing on these pathways could provide a promising way to enhance treatment results. Objective: This review aims to provide insights into enhancing antiepileptic therapy through the development of nanoformulations of synthetic and herbal drugs. Methods: A comprehensive review of existing literature was conducted to evaluate the potential of nanoformulations in improving the delivery and efficacy of antiepileptic drugs. The review covers the pathophysiological hypotheses of epilepsy, including the glutamatergic, GABAergic, oxidative stress, and neuroinflammation hypotheses, and examines the role of neurotransmitter imbalances in seizure activity. Results: Nanoformulations offer promising advantages for epilepsy treatment by enhancing drug delivery across the blood-brain barrier, reducing required dosages, and minimizing side effects. The utilization of nanoparticles can improve the bioavailability and targeting of AEDs, potentially leading to better seizure control. However, challenges such as ensuring biocompatibility and optimizing nanoparticle characteristics remain. Conclusion: While significant progress has been made in understanding epilepsy and developing treatments, the disorder continues to pose challenges. Nanoformulations represent a promising area of research that could lead to more effective and targeted therapies for epilepsy, although further studies are needed to address the associated challenges and fully realize their potential.

Long-term phenobarbital treatment is effective in working-age patients with epilepsy in rural Northeast China: a 10-year follow-up study

IntroductionEffective management of epilepsy in working-age patients is essential to reduce the burden on individuals, families, and communities. This study aimed to assess the long-term efficacy of phenobarbital (PB) in working-age patients with epilepsy in rural Northeast China and identify the risk factors for seizures during treatment.MethodsPatients aged 18–65 years diagnosed with convulsive epilepsy in rural areas of Jilin Province between 2010 and 2024 were included, and demographic and clinical data were recorded. Seizure frequency, self-efficacy, adherence, and adverse events (AEs) were assessed monthly.ResultsOf the 3,568 participants, 288 (8.1%) withdrew from the study and 159 (4.5%) died. During the first year of treatment, 75.2% of patients experienced a ≥50% reduction in seizure frequency compared with baseline (considered as treatment effectiveness); 53.7% of patients were seizure-free. By the tenth year, 97.7% of patients showed treatment effectiveness, and 89.6% were seizure-free. Self-efficacy was improved in 37.8% of patients in the first year and in 72% of patients by the tenth year. The independent risk factors for seizures during treatment were higher baseline seizure frequency [odds ratio (OR) = 1.431, 95% confidence interval (CI): 1.122–1.824], presence of multiple seizure types (OR = 1.367, 95% CI: 1.023–1.826), and poor adherence (OR = 14.806, 95% CI: 3.495–62.725), with significant differences observed in the first, third, and fifth years. The most commonly reported AEs were drowsiness (43.3%), dizziness (25.0%), and headaches (17.0%), most of which were mild and decreased over time. Age at enrollment was the only factor influencing withdrawal (hazard ratio = 0.984, 95% CI: 0.973–0.996, p = 0.010), with a substantial number of patients who withdrew (32.6%) relocating for work. Cardiovascular disease was the primary cause of death, and age at enrollment was the only risk factor (hazard ratio = 1.026, 95% CI: 1.009–1.043, p = 0.002).DiscussionWorking-age adults with epilepsy demonstrated a favorable response and tolerability to PB monotherapy. Baseline seizure frequency, seizure type, and adherence consistently predicted prognosis throughout the treatment period. Withdrawal was mainly explained by work-related pressures in this age group. Therefore, it is essential to implement interventions that support patient adherence to therapy and maintain stable regimens.

Adverse events associated with carbamazepine: a pharmacovigilance study using the FDA Adverse Event Reporting System

ABSTRACT Introduction Carbamazepine (CBZ) is a commonly used antiseizures medications (ASM), but its adverse drug reactions (ADRs) can impact the successful management of epilepsy. There are currently limited systematic studies on ADRs related to CBZ, necessitating further investigation. Areas covered Using the FDA Adverse Event Reporting System (FAERS) database , we extracted reports where CBZ was the primary suspect, conducting subgroup analyses stratified by sex and age. Four risk signal detection methods ROR, PRR, BCPNN, and EGBM were employed to systematically analyze the ADRs associated with CBZ. Expert opinion In the epilepsy population, ADRs related to CBZ often involve examinations, hereditary disorders, and infections. Subgroup analysis showed differences in ADR signals among male, female, elderly, and young patients. Human Herpesvirus 6 Infection and Dermatitis Exfoliative were consistent CBZ-induced ADRs, unaffected by age or sex. The study also identified previously overlooked ADRs such as bone metabolism abnormalities, ocular toxicity, and ototoxicity. Many ADRs linked to CBZ remain underreported. It is crucial to enhance monitoring and information dissemination about CBZ use in epileptic patients. Adjusting medication regimens for high-risk individuals, potentially incorporating acupuncture, traditional Chinese medicine, or alternative anti-seizure medications, should be considered when necessary.

Empagliflozin modulates seizure activity and oxidative stress in rats with epilepsy

Drug-resistant epilepsy, a commonly devastating condition, affects more than 50 million people globally. Type 2 diabetes mellitus (T2DM) is associated with an increased risk of neurological disorders, and a potential association between epilepsy and subsequent T2DM has emerged. Inhibiting sodium-glucose linked transporters (SGLTs), which are differentially expressed in the brain, has been shown to reduce epileptic episode activity. This study aimed to evaluate the anticonvulsive effect of empagliflozin in rats with seizures induced by maximal electric shock (MES) and pentylenetetrazol (PTZ). Generalized tonic‒clonic seizures were induced in the rats using an electroconvulsive meter, and pentylenetetrazol was injected to induce absence seizures. The duration of all the stages of seizure and Racine stage scoring (RSS) were performed. Malondialdehyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) levels in the brain tissues were determined. Histopathological analysis of the brain tissues was carried out. A significant (p <0.01) decrease in the duration of tonic hind limb extension (THLE), a significant decrease in the levels of pro-oxidants such as MDA and NO, and an increase in the levels of antioxidants such as GSH were observed in the low dose 10 mg/kg and high dose 20 mg/kg empagliflozin groups compared to the disease control group. Histopathological analysis revealed a greater number of healthy neurons with few dark-stained cells in the treatment groups, suggesting the neuroprotective effect of empagliflozin. The present study showed that empagliflozin modulates epileptic activity. Empagliflozin has a potential role in the management of epilepsy in diabetic patients.

Unraveling Epilepsy: Investigating stem cell approaches for innovative treatment and future cure

Epilepsy is a persistent neurological disorder characterized by repeated, spontaneous seizures that arise without a specific cause. These seizures result from abnormal electrical activity in the brain, leading to a range of symptoms, from brief periods of unconsciousness or minor sensory disturbances to severe convulsions. The management of epilepsy remains a significant challenge, as current treatment modalities, primarily involving antiepileptic drugs and surgical interventions to remove seizure foci, often provide adequate control for a substantial portion of patients. For this reason, stem cell therapies have become a hopeful approach because of their ability to potentially restore and renew impaired neural networks, which is particularly relevant for neurological disorders like epilepsy. This review investigates the present state of stem cell therapies in epilepsy, analyzing distinct types of stem cells, their mode of action, preclinical and clinical trials, as well as future research prospects.

Developing guidelines for nursing management of epilepsy in Ghanaian schools

BackgroundThe absence of guidelines for the nursing management of individuals living with epilepsy, who are students in Ghana, has resulted in the high dropout rates of such students. It is our hope, that in the near future, these individuals living with epilepsy will receive the needed attention, experience less stigmatization and discrimination. This, we expect, will result in better retention of such students in schools, improved academic performance and successful graduation. To achieve this, there is the need to develop appropriate guidelines and implement same for their benefit. In line with this, the study aims to develop guidelines for nurses to manage individuals living with epilepsy in Ghanaian schools.MethodologyQualitative approach will be adopted to conduct this study in two phases. In the first phase, a case study design will be deployed in the Twifo Atti-Morkwa District of the Central Region of Ghana. The case is the nursing management of individuals living with epilepsy within the school context, and the sources of information will be the general nurses, psychiatric, or community psychiatric nurses working at the schools. Within the context of the case, parents or guardians of individuals living with epilepsy in the schools as well as their teachers will be included in the study. Data will be collected through individual interviews for nurses and parents while focus group discussions will be used for the teachers. Thematic analysis will be used to analyze the data. In the second phase, guidelines will be developed using the modified e-Delphi Technique. The study will be piloted in the Komenda-Edina-Eguafo-Abrem Municipality of the Central Region of Ghana. Ethics approval for this study has been obtained from the Ethical Review Committee of the University of Pretoria in South Africa. Additionally, Administrative approvals have been obtained from the Ghana Education Service.DiscussionThe guidelines developed will form the basis for nursing management of individuals living with epilepsy in Ghanaian schools. This will help to improve educational outcomes for the individuals living with epilepsy.

Generative AI with WGAN-GP for boosting seizure detection accuracy.

Imbalanced datasets pose challenges for developing accurate seizure detection systems based on electroencephalogram (EEG) data. Generative AI techniques may help augment minority class data to facilitate automatic epileptic seizure detection. This study investigates the impact of various data augmentation (DA) approaches, including Wasserstein Generative Adversarial Network with Gradient Penalty (WGAN-GP), Vanilla GAN, Conditional GAN (CGAN), and Cramer GAN, on classification performance with Random Forest models. The best-performing GAN variant, WGAN-GP, was then integrated with a bidirectional Long Short-Term Memory (LSTM) architecture and compared against traditional and synthetic oversampling methods. The evaluation of different GAN variants for data augmentation with Random Forest classifiers identified WGAN-GP as the most effective approach. The integration of WGAN-GP with bidirectional LSTM yielded substantial performance improvements, outperforming traditional oversampling methods and achieving an accuracy of 91.73% on the augmented data, compared to 86% accuracy on real data without augmentation. The proposed generative AI approach combining WGAN-GP and recurrent neural network models outperforms comparative synthetic oversampling methods on metrics relevant for reliable seizure detection from imbalanced EEG datasets. Incorporating the WGAN-GP generative AI technique for data augmentation and integrating it with bidirectional LSTM elevates seizure detection accuracy for imbalanced EEG datasets, surpassing the performance of traditional oversampling and class weight adjustment methods. This approach shows promise for improving epilepsy monitoring and management through enhanced automated detection system effectiveness.

Expert opinion on use of vagus nerve stimulation therapy in the management of pediatric epilepsy: a Delphi consensus study

Purpose: To provide consensus-based recommendations for use of vagus nerve stimulation (VNS) therapy in the management of pediatric epilepsy. Methods: Delphi methodology with two rounds of online survey was used to build consensus. A steering committee developed 43 statements related to pediatric epilepsy and the use of VNS therapy, which were evaluated by a panel of 12 neurologists/neurosurgeons with expertise in pediatric epilepsy, who graded their agreement with each statement on a scale of 1 (“I do not agree at all”) to 5 (“I strongly agree”). For each statement, consensus was established if ≥70% of the agreement scores were 4 or 5 and <30% were 1 or 2 in the final survey. Results: Twenty-four statements regarding the need for seizure reduction in pediatric epilepsy, the recommended treatment algorithm, the benefits and safety of VNS therapy, management of side effects of VNS therapy, patient selection for VNS therapy, and the use, dosing, and titration of VNS therapy achieved consensus. VNS and other neuromodulation therapies should be considered for pediatric patients with drug-resistant epilepsy who are not candidates for resective surgery, or who do not remain seizure free after resective surgery. When VNS therapy is initiated, the target dose range should be achieved via the fastest and safest titration schedule for each patient. Scheduled programming can be helpful in dose titration. Conclusion: The expert consensus statements represent the panelists’ collective opinion on the best practice use of VNS therapy to optimize outcomes in the management of pediatric epilepsy.

Italian report on RARE epilepsies (i-RARE): A consensus on multidisciplinarity.

Rare and complex epilepsies encompass a diverse range of disorders characterized by seizures. We aimed to establish a consensus on key issues related to these conditions through collaboration among experienced neurologists, neuropediatricians, and patient advocacy representatives. Employing a modified Delphi method, a scientific board comprising 20 physicians and 4 patient advocacy representatives synthesized existing literature with their expertise to formulate statements on contentious topics. A final 32-member expert panel, representing diverse regions of Italy, validated these statements through a two-round voting process, with consensus defined as an average score ≥7. Sixteen statements reached a consensus, emphasizing the necessity for epidemiological studies to ascertain the true prevalence of rare epilepsies. Etiology emerged as a crucial factor influencing therapeutic strategies and outcome prediction, with particular concern regarding prolonged and tonic-clonic seizures. The importance of early implementation of specific drugs and non-pharmacological interventions in the treatment algorithm for developmental and epileptic encephalopathies (DEEs) was underscored. Multidisciplinary care involving experts with diverse skills was deemed essential, emphasizing non-seizure outcomes in adolescence and adulthood. This national consensus underscores the imperative for personalized, comprehensive, and multidisciplinary management of rare epilepsies/DEEs. It advocates for increased research, particularly in epidemiology and therapeutic approaches, to inform clinical decision-making and healthcare policies, ultimately enhancing patients' outcomes. The modified Delphi method is broadly used to evaluate debated topics. In this work, we sought the consensus on integrated and social care in epilepsy management. Both representatives of high-level epilepsy centers and patients' caregivers were directly involved.

A Review of Hyperventilation Activation in Diagnosis and Management of Childhood Absence Epilepsy.

Childhood absence epilepsy is one of the most prevalent pediatric epilepsy syndromes, but diagnostic delay is common and consequential. Childhood absence epilepsy is diagnosed by history and physical examination including hyperventilation with electroencephalography (EEG) used to confirm the diagnosis. Hyperventilation produces generalized spike-wave discharges on EEG in >90% of patients with childhood absence epilepsy and provokes clinical absence seizures consisting of brief loss of consciousness typically within 90 seconds. Child neurologists report a high volume of referrals for children with "staring spells" that strain already limited health care resources. Resources are further strained by the use of EEG for monitoring antiseizure medication effectiveness with unclear benefit. In this review, we examine the safety and efficacy of hyperventilation activation as a tool for the diagnosis and management of childhood absence seizures.

Pro-Ictal EEG Scheduling Improves the Yield of Epilepsy Monitoring: Validating the Use of Multiday Seizure Cycles to Optimize Video-EEG Timing.

A significant challenge of video-electroencephalography (vEEG) in epilepsy diagnosis is timing monitoring sessions to capture epileptiform activity. In this study, we introduce and validate "pro-ictal EEG scheduling", a method to schedule vEEG monitoring to coincide with periods of increased seizure likelihood as a low-risk approach to enhance the diagnostic yield. A database of long-term ambulatory vEEG monitoring sessions (n = 5,038) of adults and children was examined. Data from linked electronic seizure diaries were extracted (minimum 10 self-reported events) to generate cycle-based estimates of seizure risk. In adults, vEEG monitoring sessions coinciding with periods of estimated high-risk were allocated to the high-risk group (n = 305) and compared to remaining studies (baseline: n = 3,586). Test of proportions and risk-ratios (RR) were applied to index differences in proportions and likelihood of capturing outcome measures (abnormal report, confirmed seizure, and diary event) during monitoring. The impact of clinical and demographic factors (age, sex, epilepsy-type, and medication) was also explored. During vEEG monitoring, the high-risk group was significantly more likely to have an abnormal vEEG report (190/305:62% vs 1,790/3,586:50% [%change = 12%], RR = 1.25, 95% confidence interval [CI] = [1.137-1.370], p < 0.001), present with a confirmed seizure (56/305:18% vs 424/3,586:11% [%change = 7%], RR = 1.63, 95% CI = [1.265-2.101], p < 0.001) and report an event (153/305:50% vs 1,267/3,586:35% (%change = 15%), RR = 1.420, 95% CI = [1.259:1.602], p < 0.001). Similar effects were observed across clinical and demographic features. This study provides the first large-scale validation of pro-ictal EEG scheduling in improving the yield of vEEG. This innovative approach offers a pragmatic and low-risk strategy to enhance the diagnostic capabilities of vEEG monitoring, significantly impacting epilepsy management. ANN NEUROL 2024.

Epidemiology and real-world management of childhood epilepsy in Japan: A descriptive study using a health claim database

IntroductionThe purpose of this epidemiological study was to assess the prevalence, comorbidities, and real-world management of childhood epilepsy to provide insights for enhancing epilepsy management and medical resource planning. Materials and methodsThe study encompassed insured individuals aged 0–17 years as of December 2018 who were registered at any point in 2018, for at least part of the year, in a Japanese health claims database spanning January—December 2018. Epilepsy was defined as a diagnosis of epilepsy based on the International Classification of Diseases, 10th Revision codes, and a claimed management fee for epilepsy or an anti-seizure medication (ASM) prescription for longer than 4 weeks. The prevalence of epilepsy, patient characteristics, including comorbidities, and management status, such as prescription of ASMs, were evaluated. ResultsAmong 1528,905 registered children, 9279 were identified as having epilepsy. The prevalence of epilepsy was the lowest at 1.97 per 1000 population (95 % confidence interval [CI] 1.80–2.15) in the 0–2-year age group and increased with age to 9.34 per 1000 population (95 % CI 8.98–9.72) in the 15–17-year age group, with a significantly higher prevalence in boys than in girls in the ≥12-year age group. ASMs were prescribed to 88.3 %–91.9 % of the patients. Moreover, 27 (0.29 %) patients underwent epilepsy surgery. The frequency of claiming intravenous ASMs and long-term electroencephalogram fees increased with a decrease in age. ConclusionsOur findings indicate that young children receive more medical resources than adolescents and that epilepsy surgery is underutilized. Further investigations will help improve the management of and develop measures against epilepsy.

User involvement in the design and development of medical devices in epilepsy: A systematic review.

This systematic review aims to describe the involvement of persons with epilepsy (PWE), healthcare professionals (HP) and caregivers (CG) in the design and development of medical devices is epilepsy. A systematic review was conducted, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligibility criteria included peer-reviewed research focusing on medical devices for epilepsy management, involving users (PWE, CG, and HP) during the MDD process. Searches were performed on PubMed, Web of Science, and Scopus, and a total of 55 relevant articles were identified and reviewed. From 1999 to 2023, there was a gradual increase in the number of publications related to user involvement in epilepsy medical device development (MDD), highlighting the growing interest in this field. The medical devices involved in these studies encompassed a range of seizure detection tools, healthcare information systems, vagus nerve stimulation (VNS) and electroencephalogram (EEG) technologies reflecting the emphasis on seizure detection, prediction, and prevention. PWE and CG were the primary users involved, underscoring the importance of their perspectives. Surveys, usability testing, interviews, and focus groups were the methods used for capturing user perspectives. User involvement occurs in four out of the five stages of MDD, with production being the exception. User involvement in the MDD process for epilepsy management is an emerging area of interest holding a significant promise for improving device quality and patient outcomes. This review highlights the need for broader and more effective user involvement, as it currently lags in the development of commercially available medical devices for epilepsy management. Future research should explore the benefits and barriers of user involvement to enhance medical device technologies for epilepsy. This review covers studies that have involved users in the development process of medical devices for epilepsy. The studies reported here have focused on getting input from people with epilepsy, their caregivers, and healthcare providers. These devices include tools for detecting seizures, stimulating nerves, and tracking brain activity. Most user feedback was gathered through surveys, usability tests, interviews, and focus groups. Users were involved in nearly every stage of device development except production. The review highlights that involving users can improve device quality and patient outcomes, but more effective involvement is needed in commercial device development. Future research should focus on the benefits and challenges of user involvement.

Impact of low-carbohydrate diet on health status: an umbrella review.

The prevalence of diet-related non-communicable diseases has increased. A low-carbohydrate diet (LCDs) is one of the most popular interventions. Several systematic reviews and meta-analyses of randomised clinical trials (RCTs) and non-RCTs have linked LCDs to the management of obesity, diabetes, cardiovascular disease, epilepsy, and cancer. However, there has been limited appraisal of the strength and quality of this evidence. To systematically appraise existing meta-analyses and systematic reviews of RCTs and non-RCTs on the effects of LCDs on different health conditions. To understand their potential efficacy, we summarised the studies' findings and assessed the strength of the evidence. A search was conducted using the PubMed database from inception to October 2021 for systematic reviews and meta-analyses of RCTs and non-RCTs investigating the association between LCDs and multiple health outcomes in humans. The Academy of Nutrition and Dietetics Quality Criteria was used for the quality assessment. In addition, the evolution of heterogeneity, strength of the included studies, and effect sizes were extracted from each systematic review and meta-analysis. Ten systematic reviews and meta-analyses were included. Of the included reviews, 70% were of positive quality, 30% were neutral, and none were negative. The majority of the studies included strength in each systematic review, and the meta-analyses were of low to medium strength. The existing literature indicates that LCDs may help promote weight reduction in adults who are obese or overweight. This conclusion is supported by the findings of studies included in the analysis, which were of low to moderate strength. Furthermore, compelling data indicates a significant association between low-carbohydrate diets (LCDs) and a reduction in haemoglobin A1c levels among those diagnosed with type 2 diabetes mellitus. In contrast, there was a lack of evidence of this correlation in type 1 diabetes mellitus patients or those with cardiovascular diseases. Additionally, there was limited evidence regarding the effectiveness of LCDs in epilepsy and adult cancer patients. This review thoroughly examines the current body of information on how LCDs affect various health outcomes. Studies have presented evidence to support the idea that incorporating LCDs can positively influence weight management and HbA1c levels. However, there is a lack of information regarding the association between LCDs and individuals with Type 1 diabetes mellitus and cardiovascular diseases. Additionally, there is limited empirical evidence to substantiate the effectiveness of LCDs in the treatment of epilepsy and adult cancer patients. The long-term effects of LCDs on mortality and other chronic diseases that account for different carbohydrate subtypes is unclear. Further longitudinal cohort studies are required to reach definitive conclusions.

HPMC Extended-Release Multi-Composite Matrix for Co-delivery of Oxcarbamazepine and Vitamin D.

Background: Carbamazepine (CBZ) is considered as first-line treatment for epilepsy. The literature has signified a history of non-uniform drug performance and clinical failures. However, many studies suggested that Oxcarbazepine (OXC), a structural analog of CBZ, may have an equivalent antiepileptic effect. OXC follows a different metabolic pathway other than CBZ. However, both share the same mechanism of action by blocking voltage-gated sodium channels. Objectives: This study aimed to form hydroxypropyl methylcellulose (HPMC) extended-release tablets containing OXC combined with vitamin D. Methods: These formulated tablets were tested for their dissolution rate, tablet hardness, friability, thickness and pharmacokinetic parameters (Cmax and Cmin). Blood sodium levels were additionally investigated to ensure the absence of hyponatremia; the main side effect of long-term use of CBZ and some of its derivatives. Results: The use of HPMC inhibited the formation of dihydrate OXC form thus offering a significant extended-release profile. OXC also showed a highlighted capability to attain high bioavailability. Microcrystalline cellulose (MCC) was also added to tablets formed to inhibit polymorphic transformation. Tablets containing OXC co-delivered with vitamin D ensured significantly decreased susceptibility to hyponatremia, and an extended-release profile was evident. Lower amounts of OXC were loaded in formed tablets containing vitamin D owing to the synergistic effect between vitamin D and antiepileptic drugs. Conclusion: Conclusively, employing these newly HPMC-constructed tablets of OXC co-delivered with vitamin D appeared to be a promising option for the effective management of epilepsy with least side effects.

Severe, uncontrolled epilepsy in pregnancy: A population-based case-control study

Background Epilepsy affects one percent of the UK population and is the most common serious neurological condition experienced during pregnancy. We compared the characteristics, clinical management, and pregnancy outcomes in women with severe, uncontrolled epilepsy to those of women with well controlled disease. Methods We conducted a population-based case-control study in all UK consultant-led maternity units. Cases of severe uncontrolled epilepsy during pregnancy were identified prospectively and reported via the UK Obstetric Surveillance System (UKOSS). Severe epilepsy was defined a-priori as ≥1 of the following: admission to hospital during pregnancy to manage seizures; prescribed ≥3 antiepileptic medications; or died from epilepsy. Controls comprised women with epilepsy not meeting the case definition, identified within the same centres as cases. Pre-pregnancy epilepsy control and pregnancy outcomes were compared between groups using multivariable logistic regression. Results We identified 94 cases between 1 October 2015 and 31 March 2017 and compared these with 186 controls. Cases were significantly more likely to be admitted to manage seizures in the year preceding pregnancy (42/94 cases vs 10/186 controls, adjusted odds ratio [aOR]=7.38 [95% CI 2.70-20.2]), and to report their most recent seizure within 3 months of pregnancy (51/94 cases vs 18/186 controls, aOR=5.86 [95% CI 2.30-15.0]). Cases were significantly more likely to deliver before 37 weeks (20/94 cases vs 8/186 controls, aOR=7.61 [95% CI 2.87-20.2]). Conclusions Women admitted for seizure management in the year before pregnancy are at higher risk of severe epilepsy during pregnancy and of preterm birth. These women should be prioritised for discussion about pregnancy and contraception. When pregnant, they should be reviewed as early as possible by specialists in the management of epilepsy during pregnancy. Delivering messages about the importance of pregnancy planning and contraception to all women with epilepsy should be viewed as the responsibility of all clinicians involved their care.

Non-pharmacological approaches to epilepsy management - dietary interventions

Non-pharmacological approaches to epilepsy management - dietary interventions

SCN1A rs6732655A/T polymorphism: Diagnostic and therapeutic insights for drug-resistant epilepsy.

A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs, resulting in heightened mortality rates, psychosocial challenges, and a diminished quality of life. Genetic factors, particularly within the SCN1A gene, and the pro-inflammatory cytokine response is important in intricating the drug resistance in idiopathic epilepsy cases. In this extended study, we determined the correlation of rs6732655A/T single nucleotide polymorphism to understand the causative association of SCN1A gene with epilepsy drug resistance and inflammatory response. To find the correlation of SCN1A gene rs6732655A/T polymorphism with the drug-resistant epilepsy and inflammatory response. The study enrolled 100 age and sex-matched patients of both drug-resistant and drug-responsive epilepsy cases. We analysed the rs6732655A/T polymorphism to study its association and causative role in drug-resistant epilepsy cases using restriction fragment length polymorphism technique. The diagnostic performance of interleukin (IL)-1β, IL-6, and high mobility group box 1 (HMGB1) protein levels was evaluated in conjunction with genotypic outcome receiver operating characteristic analysis. AT and AA genotypes of rs6732655 SCN1A gene polymorphism were associated with higher risk of drug resistance epilepsy. Serum biomarkers IL-6, IL1β and HMGB1 demonstrated diagnostic potential, with cutoff values of 4.63 pg/mL, 59.52 pg/mL and 7.99 ng/mL, respectively, offering valuable tools for epilepsy management. Moreover, specific genotypes (AA and AT) were found to be linked to the elevated levels of IL-1β and IL-6 and potentially reflecting increased oxidative stress and neuro-inflammation in drug-resistant cases supporting the previous reported outcome of high inflammatory markers response in drug resistance epilepsy. SCN1A genotypes AA and AT are linked to higher drug-resistant epilepsy risk. These findings underscore the potential influence of inflammation and genetics on epilepsy treatment resistance.