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Background Pediatric epilepsy presents challenges in treatment optimization, with a significant proportion of patients experiencing inadequate seizure control despite anti-seizure medications (ASMs) therapy. Recent research has indicated the involvement of neuroinflammation and immune-mediated mechanisms in epilepsy pathogenesis, suggesting a potential interplay between immunological factors and ASMs responsiveness. This study aimed to investigate the role of immunological factors in pediatric generalized, focal epilepsy and their interaction with ASMs mechanisms to understand their potential influence on treatment outcomes. Methods A retrospective cohort study was conducted involving 136 pediatric epilepsy patients, categorized into Anti-seizure medications Insensitive Group ( n  = 67) and Anti-seizure medications Sensitive Group ( n  = 69). Immunoglobulin levels and immunological factors, including cytokines, were assessed before treatment. Seizure characteristics and ASMs levels were also analyzed. Associations between immunological factors, seizure characteristics, and ASMs sensitivity was evaluated. Results The study revealed significant differences in immunological factors, including interleukin-6 (IL-6), IL-1β and IL-10 levels, between the insensitive and sensitive groups. Furthermore, seizure frequency, drug-resistant seizures, seizure severity, seizure-free period, and status epilepticus all demonstrated significant correlations with the sensitivity to ASMs, with negative correlations for seizure frequency, drug-resistant seizures, seizure severity, and positive correlations for seizure-free period and status epilepticus. Conclusion The study highlights the complex interplay between immune function, seizure characteristics, and ASMs mechanisms, underscoring the need for a comprehensive understanding of the immunological modulation of drug response in pediatric epilepsy. Clinical trial number Not applicable.

Background Oxidative damage has been implicated in multiple neurodegenerative diseases, including epilepsy. Selenium, in the form of selenoproteins is an integral part of the human antioxidant defense system. Though a relationship between the altered selenium levels and epilepsy has been reported, limited evidence is available about the expression pattern of selenoproteins in epileptic patients. Objective This study aimed to determine the serum selenium levels in idiopathic epileptic and healthy individuals. Expression profiling of selenoproteins (GPx1, TRxR1 and SEPW1) both at mRNA and protein levels was also evaluated. Methods Serum selenium levels of 30 patients with idiopathic generalized epilepsy and their age and gender matched 30 healthy controls were measured. Protein levels of Serum Glutathione Peroxidase 1 (GPx1), Thioredoxin Reductase 1 (TRxR1) and Selenoprotein W (SEPW1) were estimated using ELISA. mRNA expression of GPx1, TRxR1 and SEPW1 were determined using qRT-PCR. Results The mean values for serum selenium levels in cases and controls were 37.6  ±  2.0 µmol/ml and 38.9  ±  2.7 µmol/ml, respectively. Selenium levels in cases were significantly lower as compared to controls ( p  = 0.031). No statistically significant differences were observed between the serum levels of selenoproteins GPx1, TRxR1 and SEPW1 in epileptic patients and the healthy group. GPx1 and TRxR1 expression was found to be down regulated (0.34 and 0.13 folds respectively) whereas SEPW 1 was found to be 0.04 folds up regulated in epileptic patients compared to the healthy subjects. Conclusion Selenium deficiency observed in epileptic patients suggests the association between serum selenium levels and epilepsy. This study provides the information about the selenium status in Pakistani population and helps in understanding the role of selenium in the prevention of epilepsy. Graphical Abstract

Objective This study evaluates the potential protective effects of statins against epilepsy, focusing on their differential impacts on focal and generalized epilepsy. It investigates the role of statins through the HMGCR gene and associated low‐density lipoprotein (LDL) cholesterol levels. Methods A two‐sample Mendelian randomization (MR) and summary‐data‐based MR (SMR) approach were employed using genetic instruments from genome‐wide association studies (GWASs) and expression quantitative trait loci (eQTLs). Subgroup analyses examined focal and generalized epilepsy, with sensitivity tests, including MR‐Egger regression and MR‐PRESSO, to assess horizontal pleiotropy and robustness. Results SMR analysis found no significant association between HMGCR expression and epilepsy risk across subtypes (p > 0.05). However, inverse‐variance‐weighted MR (IVW‐MR) showed that elevated LDL cholesterol mediated by HMGCR was linked to an increased risk of focal epilepsy (OR = 1.251, 95% CI = 1.135–1.378). No such association was observed for generalized epilepsy. Statins showed promise in reducing post‐stroke epilepsy risk, likely through anti‐inflammatory and neuroprotective effects. Significance The findings suggest that statins' protective effects may be subtype‐specific, particularly in post‐stroke focal epilepsy. Further research is needed to elucidate underlying mechanisms and optimize their therapeutic potential in epilepsy management. Plain Language Summary Statins, drugs typically used to manage cholesterol, may also lower the risk of developing certain types of epilepsy, especially post‐stroke focal epilepsy, by reducing inflammation and protecting brain cells. The research found no clear effect of statins on generalized epilepsy or epilepsy caused by other factors. These results could aid in creating better treatments for epilepsy in the future.

Objective Understanding the role of plasma proteins in the pathophysiology of epilepsy is crucial for uncovering novel biological mechanisms and therapeutic targets. Mendelian randomization (MR) provides a valuable tool for dissecting potentially causal associations between circulating proteins and disease risk. This study aimed to systematically assess potential causal relationships between the plasma proteome and epilepsy. Methods We implemented a multistage MR framework using genetic instruments for 4907 plasma proteins. Following rigorous quality control and instrument selection, a proteome‐wide, two‐sample MR analysis was performed against three epilepsy phenotypes (epilepsy, generalized epilepsy (GE), and focal epilepsy (FE)). Proteins showing nominal significance were further evaluated using Summary‐data‐based MR (SMR) and colocalization analysis to probe for a shared genetic basis. We additionally incorporated analyses using alternative pQTL resources to evaluate the robustness of our findings. Results Our proteome‐wide screen identified several candidate proteins associated with epilepsy risk at a nominal significance threshold (P‐IVW < 0.01). SMR analysis provided support for candidates across the epilepsy subtypes, including CRABP2 and CD300C for epilepsy, GM2A for FE, and PCBD1 for GE. However, subsequent colocalization analysis did not yield strong evidence for a shared causal variant for any candidate, with some showing only moderate evidence (e.g., ACVRL1), underscoring a complex genetic architecture and the need for cautious interpretation. Supplementary analyses based on UKB‐PPP pQTLs paired with FinnGen genome‐wide association studies (GWAS) showed several nominal associations but limited overlap with the deCODE–FinnGen results. Significance Our exploratory assessment of the plasma proteome did not identify definitively causal proteins but did generate a prioritized list of candidates potentially linked to epilepsy. Proteins such as CRABP2, CD300C, GM2A, and PCBD1, which are involved in relevant neurodevelopmental, immune, and metabolic pathways, represent valuable leads for future experimental validation. By comparing results across different pQTL datasets, we also highlight the importance of replication and cross‐resource validation in future epilepsy research. Plain Language Summary Epilepsy is a common brain disorder, but its exact causes are often unknown. Our study used genetic data to investigate if thousands of proteins circulating in the blood have a causal effect on epilepsy risk. While we did not pinpoint a single definitive protein, we identified several promising candidates, such as CRABP2, CD300C, GM2A, and PCBD1, that may be linked to epilepsy risk. We also repeated the analysis using an additional protein dataset, which yielded some different results, showing that findings can vary depending on the data source. These findings provide valuable new leads for understanding epilepsy and developing future therapies.

Reproductive endocrine disorders occur more frequently among women and men with epilepsy than among normal subjects 1 – 3 . In women these disorders have generally been attributed to the epilepsy itself, 2 , 3 rather than to any antiepileptic treatment. Both partial and generalized seizures, and perhaps interictal epileptic discharges as well, can increase the secretion of various pituitary hormones, such as gonadotropins and prolactin, 4 – 6 and alter, perhaps even permanently, the function of the hypothalamic-pituitary-gonadal axis 2 , 3 . Antiepileptic-drug therapy is associated with changes in the serum concentrations of sex hormones. Antiepileptic medications that induce liver enzymes also increase the serum concentrations . . .

This study was specifically aimed to evaluate the sexual and reproductive health in a group of men with generalized epilepsy. In total, 44 men with generalized epilepsy were included in this study, their ages between 18 and 48 years (29.2±9.9) and duration of illness between 2 and 35 years (11.2±7.4); 34 patients were treated with conventional antiepileptic drugs (AEDs). Sexological and psychological interviews together with serum total testosterone, E 2 , FSH, LH and prolactin were determined. Hyposexuality was diagnosed in 61.4%. Erectile dysfunction (ED) and premature ejaculation represented 70.4 and 66.7%, respectively. Variables such as hyposexuality, seizure duration and its poor control on AEDs were significantly associated with depressive symptoms. Compared to the normal control group, all patients reported elevated E 2 levels ( P <0.001), 10 had FSH ( n =4) and LH ( n =6) levels exceeding that of the normal range for controls and two had hyperprolactinemia. Although the patients’ mean value of total testosterone remained within the normal range, but it was significantly lower in hyposexual men compared to nonhyposexual ( P <0.002), only two epileptic patients had markedly reduced level of total testosterone beyond normal control levels. This study strongly supports that: (1) The risk of hyposexuality and reproductive disturbances is high in epileptic patients with GTC convulsions despite the AEDs utilized. The risk for SD is further increased by poor seizure control and the frequently accompanied depressive manifestations. (2) It is possible that elevated E2 could increase the risk of SD by reducing active testosterone through negative feedback and the reduction of active testosterone could increase seizure intractability to antiepileptic medications.

The aim of the present work was to perform a comparative assessment of the efficacy and safety of traditional and contemporary antiepileptic agents in women of reproductive age. The experimental group consisted of 65 patients, of whom 48 had partial epilepsy and 17 had idiopathic generalized epilepsy. A number of issues were addressed in studies of a larger group of patients (110), including both women (65) and men (45). The following agents were studied: Topamax, valproates, carbamazepine, and barbiturates, all used as monotherapy. Patients’ status was evaluated using clinical (neurological, psychiatric), psychometric, neuropsychological, and hormonal parameters. The data led to the general conclusion that Topamax had advantages over the other study agents in the treatment of women with epilepsy.

The amino group has a pKa value of about 6.5 and chitosan acts a positively charged polymer that binds to the negatively charged lipids in the gastrointestinal tract, preventing their absorption. 2 3 We think that the anionic carboxyl group of the lipophilic valproate may attach to the positive charged tertiary amino group of chitosan so that it is extracted rather than absorbed, resulting in a lowering of its serum concentration.

Canine idiopathic epilepsy (IE) is a common neurological disease with severe impact on the owner´s and the dog's quality of life. A subpopulation of dogs with IE does not respond to antiseizure drugs (non-responder). Th17 cells (T helper cells) and their proinflammatory Interleukin-17 (IL-17) are part of the immune system and previous studies showed their involvement in the pathogenesis of several autoimmune diseases. Non-responder might have an abnormal immune response against structures of the central nervous system. To discover a new aetiology of canine IE and thereby optimising the therapy of intractable IE, this prospective study aimed to investigate Th17 cells and IL-17 in dogs with IE. The underlying hypothesis was that in some dogs with IE a Th17 cell-mediated immune response could be detectable. 57 dogs with IE and 10 healthy dogs (control group, C) were enrolled in the study. EDTA blood was taken to measure Th17 cells by flow cytometry. IL-17 was measured in 35 cerebrospinal fluid (CSF) and 33 serum samples using an enzyme-linked immunosorbent assay (ELISA). It was investigated whether there was a significant increase of stimulated Th17 cells in blood samples or of IL-17 in serum and CSF samples of dogs with IE in comparison to C. Correlations between the amount of Th17 cells/μL or IL-17 and different clinical parameters e.g. seizure frequency, seizure type, seizure severity or treatment response were evaluated. Additionally, Th17 cells/μL were randomly controlled of 17 dogs with IE and were examined for changes over time and in relation to treatment response. Ten dogs with IE had strongly elevated stimulated Th17 cells/μL within the blood (>100 Th17 cells/μL). A slight positive correlation between stimulated Th17 cells/μL and seizure severity (p = 0.046; rSpear = 0.27) was proven in these dogs. In addition, 4/10 dogs with elevated Th17 levels experienced cluster seizures and status epilepticus in comparison to 9% of the dogs with non-elevated Th17 levels (<100 Th17 cells/μL). Dogs with IE had significantly higher IL-17 values in CSF and serum samples compared to C (p<0.001; p<0.002; respectively). In single dogs with IE, strongly increased amounts of Th17 cells were detectable and dogs with elevated Th17 cells seemed to have a greater risk for experiencing a combination of cluster seizures and status epilepticus. Therefore, an underlying Th17-cell mediated immune response was suspected and hence anti-inflammatory drugs could be indicated in these single cases with intractable epilepsy.