Search Results (312)

Objective: The interactions between the central nervous system (CNS) and the immune system suggest that immune mechanisms may be effective in the pathogenesis of epilepsy and epileptic seizures. Although studies on the natural immune response and epilepsy are continuing, it is not yet clear whether the interaction of the current immune system is due to epilepsy itself or antiepileptic drugs (AEDs), since epileptic patients also use AEDs There are a limited number of studies that have reported an increased incidence of upper respiratory tract infections (URTIs) in patients during levetiracetam (LEV) treatment. Therefore, we aimed to report our experience regarding the effect of LEV monotherapy on the complete blood count (CBC), immunoglobulin (Ig) levels, and lymphocyte subgroups in the interictal period in children and adolescents with epilepsy. Methods: This study enrolled 31 children who presented with epilepsy and underwent LEV monotherapy for at least one year (patient group) and 43 healthy children (control group). The CBC parameters (hemoglobin (hb), lymphocytes, leukocytes, neutrophils, and platelets), Ig levels (IgA, IgM, IgG, and IgE), and lymphocyte subsets (CD3, CD4, CD8, CD4/CD8 ratio, CD19, CD56, NKT cells, and Treg cells) were measured and compared between the two groups. The patients were also investigated regarding the frequency and types of infections that they experienced in the first month and first year of the study, and these data were compared between the patient group and the control group. In addition, the same parameters and the frequency of infection were compared among the patient subgroups (focal and generalized seizures). Results: The results of the present study indicate that there were no significant differences in the CBC parameters, lymphocyte subsets, or Ig levels between the patient group and the control group. The comparison among the patient subgroups was similar; however, the CD4/CD8 ratio was lower in the patient subgroup with focal seizures. In addition, there were no significant differences in the frequency or type of infections experienced one month and one year of the study between the patient group and the control group, and likewise for the patient subgroups (focal and generalized seizures). Conclusions: The present study demonstrated that LEV monotherapy did not increase the incidence of infection, and there were no significant effects on the CBC or on the humoral or cellular immune system in epileptic children. These findings also suggest that the CD4/CD8 ratio among lymphocyte subgroups is lower in patients with focal seizures. However, the epilepsy subgroups had a relatively small sample size; therefore, further prospective studies involving a larger patient population are needed to establish the association between LEV monotherapy and lymphocyte subgroups in patients with epilepsy. Full article

Background: Hypometabolism of the thalamus has been reported in epilepsy patients. This study aimed to investigate the prognostic value of thalamic metabolic activity in children with epilepsy. Methods: A total of 200 children with epilepsy and 237 children without epilepsy (sex- and age-matched control group) underwent 18F-FDG PET/CT in this study. Localization of the interictal hypometabolic epileptic focus was performed visually. Bilateral thalamic metabolic activity was evaluated qualitatively (thalamic FDG uptake in relation to the cerebral cortex) and semi-quantitatively (SUV max, normalized SUV (ratio to ipsilateral cerebellum), and absolute asymmetric index (AAI). Results: A total of 133 patients (66.5%) with epilepsy showed cerebral cortical hypometabolism in the interictal 18F-FDG PET study; there were 76 patients on the right side, 55 patients on the left side, and two patients on both sides. Of these 133 patients, 45 also had visually observed asymmetric hypometabolism in the thalamus. Semi-quantitatively, asymmetry was more prominent in epileptic patients. AAI was a more sensitive variable than other variables. Average AAIs were 3.89% and 7.36% in the control and epilepsy patients, respectively. Metabolic activity in the thalami was significantly reduced in epileptic patients compared to the control group. Associated hypometabolism of the ipsilateral thalamus was observed in 66.5% of epileptic patients with a focal cortical defect semi-quantitatively. Overall, 61 out of 200 patients showed thalamus hypometabolism. Some 51 out of 61 patients (83.6%) with thalamus hypometabolism showed refractory disease; however, the refractory disease was noted in 90 out of 139 (64.7%) patients without thalamus hypometabolism. Brain surgery was performed in 86 epileptic patients (43%). Some 35 out of 86 patients had thalamus hypometabolism. Recurrence of epilepsy was observed more in patients with thalamus hypometabolism (48% vs. 25%), with p ≤ 0.01. Conclusion: This study suggests that patients with thalamus metabolic abnormalities may be more medically resistant to therapy and less responsive to surgical treatments. Therefore, the thalamus metabolic abnormality could be used as a prognostic sign in pediatric epilepsy. Recent studies have also suggested that incorporating thalamic metabolic data into clinical workflows may improve the stratification of treatment-resistant epilepsy in children. Full article

Objectives: The primary objective of this study was to determine whether motor disorders are significantly more prevalent in children with Autism Spectrum Disorder (ASD) without co-occurring genetic or neurological conditions compared to neurotypical children. Another aim was to explore the applicability of the MABC-2 test for assessing motor skills in a Polish cohort of children with ASD. Additionally, this study sought to develop a basic framework for motor skill assessment in children with autism. Methods: This study included 166 Caucasian children, both sexes, aged 5–12 years, without intellectual disability (IQ ≥ 70), without concomitant genetic or neurological disorders, particularly epilepsy or cerebral palsy. The study group consisted of children with ASD (n = 71), and the control group consisted of neurotypical children (n = 95). The participants were assessed with the Movement Assessment Battery for Children–second edition (MABC-2), MABC-2 checklist and the Developmental Coordination Disorder Questionnaire (DCDQ), used as a reference point. Results: The children with ASD obtained significantly lower MABC-2 test results in all subtests in comparison with the control group. The children with suspected or diagnosed coordination disorders were characterized by a significantly greater number of co-occurring non-motor factors than the other participants of this study. MABC-2 test showed greater consistency with DCDQ than with the MABC-2 questionnaire. Conclusions: Children with ASD present a lower level of manual dexterity and balance and greater difficulties in performing tasks, including throwing and catching, in comparison with neurotypical children. The MABC-2 test with the MABC-2 checklist and DCDQ questionnaire constitute a complementary diagnostic tool. Full article

Background/Aim: Dental treatment is typically performed under general anesthesia for children who have difficulty cooperating, as well as for those with mental or physical disabilities requiring special care. This study aims to categorize and evaluate the systemic disease or syndrome status, age, and gender of children who require dental treatment under general anesthesia. Materials and Methods: In this study, the ages, sexes, disabilities (if any), and systemic diseases of patients requiring dental treatment under general anesthesia (GA) between the ages of 1 and 15 were analyzed. The patients were categorized based on having difficulties cooperating or having mental or physical disabilities that require special care. Results: In this study, data from 1666 patients were examined. A total of 955 patients (57.32%) were male, while 711 (42.67%) were female. Overall, 232 (13.9%) patients with disabilities or systemic diseases visited the clinic, including 49 who had epilepsy (2.9%), the highest number among the systemic disease group. This finding was statistically significant in the 4–6 age group (p < 0.00). Conclusions: Among patients with special needs, epilepsy emerged as a disorder that requires the most dental treatment. We believe that providing dental treatment for children with neurological diseases, such as epilepsy, in a fully equipped operating room will be beneficial in managing complications that may arise during treatment. Full article

Hemolytic uremic syndrome (HUS), a thrombotic microangiopathy primarily affecting the kidneys, can also involve the central nervous system (CNS), often leading to significant morbidity and mortality. Neurologic manifestations are among the most severe extra-renal complications, particularly in children and during outbreaks of Shiga toxin-producing Escherichia coli (STEC)-associated HUS (typical (tHUS)). This review explores the clinical spectrum, pathophysiology, diagnostic workup, and age-specific outcomes of neurologic involvement in both typical (tHUS) and atypical (aHUS). Neurologic complications occur in up to 11% of pediatric and over 40% of adult STEC-HUS cases in outbreak settings. Presentations include seizures, encephalopathy, focal deficits, movement disorders, and posterior reversible encephalopathy syndrome (PRES). Magnetic resonance imaging (MRI) commonly reveals basal ganglia or parieto-occipital lesions, though subtle or delayed findings may occur. Laboratory workup typically confirms microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and kidney damage, with additional markers of inflammation or metabolic dysregulation. Eculizumab is the first-line treatment for aHUS with CNS involvement, while its utility in STEC-HUS remains uncertain. Although many children recover fully, those with early CNS involvement are at greater risk of developing epilepsy, cognitive delays, or fine motor deficits. Adults may experience lingering neurocognitive symptoms despite apparent clinical recovery. Differences in presentation and imaging findings between age groups emphasize the need for tailored diagnostic and therapeutic strategies. Comprehensive neurorehabilitation and long-term follow-up are crucial for identifying residual deficits. Continued research into predictive biomarkers, neuroprotective interventions, and standardized treatment protocols is needed for improving outcomes in HUS patients with neurological complications. Full article

Background: Developmental delay and intellectual disability (DD/ID) are frequently accompanied by epilepsy, and growing evidence implicates variants in voltage-gated calcium channel genes in their pathogenesis. This study aimed to investigate the association of polymorphisms in CACNA1A, CACNA1C, and CACNA1H with DD/ID and epilepsy comorbidity in Korean children. Methods: We retrospectively analyzed 141 pediatric patients diagnosed with DD/ID who underwent whole-exome sequencing (WES) and were not found to have pathogenic monogenic variants. Nine single-nucleotide polymorphisms (SNPs) across CACNA1A, CACNA1C, and CACNA1H were selected based on functional annotation scores and prior literature. Genotype data were extracted from WES variant files, and allele and genotype frequencies were compared with control data from the gnomAD East Asian population and the Korean Reference Genome Database (KRGDB). Subgroup analyses were performed according to epilepsy comorbidity. Results: The CACNA1A rs16023 variant showed a significantly higher B allele frequency in DD/ID patients than in both control datasets and was also associated with epilepsy comorbidity. Genotype distribution analysis revealed that the BB genotype of rs16023 was more frequent in patients with epilepsy. Conclusions: The CACNA1A rs16023 variant may contribute to genetic susceptibility to DD/ID and epilepsy in Korean children, potentially through regulatory mechanisms. These findings support the relevance of calcium channel genes in neurodevelopmental disorders and highlight the importance of integrating functional annotation in variant prioritization. Full article

Epilepsy affects over 12 million children worldwide, with approximately 30% classified as having drug-resistant epilepsy (DRE), often accompanied by neuropsychiatric comorbidities that severely impact quality of life. The endocannabinoid system (ECS) functions as a multifaceted neuromodulatory network regulating neuronal excitability, synaptic plasticity, and immune homeostasis from early life through adolescence and into aging. In pediatric epilepsies, alterations in ECS components, particularly CB1 receptor expression and endocannabinoid levels, reveal disorder-specific vulnerabilities and therapeutic opportunities. Cannabidiol (CBD), a non-psychoactive compound from Cannabis sativa, has shown strong preclinical and clinical efficacy in treating DRE and is approved for Dravet syndrome, Lennox–Gastaut syndrome, and Tuberous Sclerosis Complex. Other ECS-based strategies, such as the use of CB1 receptor-positive allosteric modulators, can selectively enhance endogenous cannabinoid signaling where and when it is active, potentially reducing seizures in conditions like Dravet and absence epilepsy. Similarly, FAAH and MAGL inhibitors may help restore ECS tone without directly activating CB1 receptors. Precision targeting of ECS components based on regional expression and syndrome-specific pathophysiology may optimize seizure control and associated comorbidities. Nonetheless, long-term pediatric use must be approached with caution, given the critical role of the ECS in brain development. Full article

Background/Objectives: This study aimed to characterize the pharmacokinetic profiles of clobazam (CLB) and its active metabolite, N-desmethylclobazam (N-CLB), by establishing a population pharmacokinetic (PPK) model in Chinese children with epilepsy to propose individualized dosing regimens that achieve better clinical outcomes. Methods: This study examined plasma samples collected from 103 pediatric patients with refractory epilepsy undergoing CLB treatment. The plasma concentrations of CLB and its active metabolite N-CLB were measured. The developmental characteristics, CYP2C19 genotype, concomitant medications, and liver and kidney function indicators of the children with epilepsy were considered potential factors affecting the pharmacokinetic characteristics of CLB and N-CLB and analyzed using a PPK modeling approach. Results: A total of 156 samples were attained for PPK model development. The pharmacokinetic profiles of CLB and N-CLB were described using a tandem one-compartment model with first-order elimination. Body weight and CYP2C19 genotype showed statistical significance for CLB and/or N-CLB clearance. The N-CLB/CLB metabolic ratios of AUC_24h, C_min, and C_max in a steady state were as follows: normal metabolizers (NMs) < intermediated metabolizers (IMs) < poor metabolizers (PMs). The final model achieved good prediction performance and stability. Monte Carlo simulations demonstrated that the trough concentrations of CLB and N-CLB in children with epilepsy could reach satisfactory target values under varying dose regimens in CYP2C19 NMs and IMs, whereas there was a failure to achieve the desired trough concentrations of CLB and N-CLB simultaneously in CYP2C19 PMs due to the accumulation of N-CLB. Conclusions: Body weight and CYP2C19 genotype had an impact on CLB and/or N-CLB clearance in children with epilepsy. To ensure safe treatment, it is recommended to use the concentration of N-CLB as the target indicator for therapeutic drug monitoring and dose adjustments in CYP2C19 PMs. These results provide evidence for guiding the precise use of CLB. Full article

Background: Oxidative stress is associated with the pathogenesis of epilepsy. Long-term treatment with anti-seizure medications (ASMs) may reduce antioxidant levels, which consequently impairs the brain’s ability to counteract oxidative damage. This study aimed to assess the concentrations of selected antioxidants (i.e., glutathione, retinol, and α- and γ-tocopherols) in children with epilepsy treated with polytherapy. Methods: The study included 21 children with epilepsy treated with ≥2 ASMs for at least 6 months (mean age 7.1 ± 4.4 years) and 23 control children without epilepsy (mean age 7.4 ± 3.9 years). Both groups were recruited at the Department of Pediatric Neurology, the Medical University of Silesia in Katowice (Poland). The concentrations of glutathione, retinol, and α- and γ-tocopherols were determined in blood serum by HPLC. The antioxidant levels were compared between sex and age subgroups of individuals with epilepsy. Results: In the group of individuals with epilepsy, the percentage of females was 38% and in the control group it was 30%. There were no differences in antioxidant levels between female and male individuals with epilepsy, nor between younger epileptic children (0–6 years) and older children (>6 years). Individuals with epilepsy had significantly lower glutathione levels than the control group (1.5 ± 0.3 µmol/L vs. 2.4 ± 1.2 µmol/L, respectively, p < 0.001). In turn, the ratios of both α-tocopherol/glutathione and γ-tocopherol/glutathione were higher in individuals with epilepsy than in the control group (p = 0.042 and p = 0.004, respectively). Individuals with epilepsy taking ASM combinations other than valproic acid (VPA) and levetiracetam (LEV) had a lower level of both retinol and glutathione than individuals on VPA and LEV treatment (for retinol 0.44 ± 0.13 µmol/L vs. 0.6 ± 0.1 µmol/L, respectively, p = 0.047, and for glutathione 1.3 ± 0.3 µmol/L vs. 1.8 ± 0.3 µmol/L, respectively, p = 0.003). In the individuals with epilepsy, the level of α-tocopherol decreased with age (r = −0.505, p = 0.019). In turn, in the control group, the levels of retinol and γ-tocopherol increased with age (r = 0.573, p = 0.004 and r = 0.461, p = 0.027, respectively). Conclusions: Glutathione levels significantly differed between children with and without epilepsy. The concentration of α-tocopherol decreased with age in pediatric individuals with epilepsy. The levels of both retinol and glutathione were higher in individuals with epilepsy taking VPA and LEV treatment compared to individuals on ASMs combination other than VPA and LEV. Full article

Background: Physical activity is essential for the physical and psychological development of children, contributing to both fitness and overall well-being. However, children with neurological conditions such as childhood absence seizures (CAE), a type of epilepsy characterized by brief episodes of impaired consciousness, may face barriers to participating in regular physical activities. This limitation can negatively affect their quality of life, motor coordination, and cognitive function. Despite this, there is limited research focusing on the physical activity levels of children with absence seizures in comparison to healthy children. Methods: This study aims to compare physical activity levels in children with absence seizures and healthy controls, using the Physical Activity Questionnaire for Children (PAQ-C), a validated tool for assessing children’s engagement in physical activity. The sample included 125 children with absence seizures and 125 healthy controls. The study also assessed anxious–depressive traits using the Children’s Depression Inventory (CDI-2) and the Multidimensional Anxiety Scale for Children (MASC-2). Additionally, seizure frequency and severity were documented for the seizure group, and the impact of different treatment regimens (levetiracetam, valproate, lamotrigine) was explored. Results: The results revealed that children with absence seizures exhibited lower physical activity levels compared to healthy children, although the difference did not reach statistical significance. Furthermore, they had higher scores for anxious–depressive traits. There were no significant differences in physical activity levels between the different treatment groups. The study also found that lower physical activity was correlated with poorer quality of life and increased psychological distress in the seizure group. Conclusion: Children with absence seizures face significant barriers to physical activity, which may be further compounded by psychological distress. These findings emphasize the need for targeted interventions to improve physical activity and address mental health concerns in this population. By enhancing physical activity levels and supporting psychological well-being, interventions can improve the quality of life and overall health of children with absence seizures. Additionally, the results highlight the importance of promoting inclusive physical activity programs for children with neurological conditions. Full article

Despite advances in technology, the overall management of type 1 diabetes mellitus (T1DM) remains suboptimal. The idea of restricting carbohydrate intake to decrease glycemic spikes and insulin requirements has been revisited in recent years. After impressive results in the fields of type 2 diabetes (T2DM) and epilepsy, low-carbohydrate (LCD) and ketogenic (KD) diets have gained renewed interest as a possible treatment option for T1DM. In this narrative review, we discuss the available data regarding LCDs and KDs in both the adult and pediatric populations. Research data is still scarce, as most studies are short-term and show considerable heterogeneity in dietary composition and patient outcomes. In general, carbohydrate restriction enhances glycemic control by reducing postprandial glucose excursions, improving time-in-range, and lowering HbA1c, with conflicting effects on other parameters such as lipid profile and body weight. Adverse effects such as hypoglycemia and diabetic ketoacidosis are rarely reported, although some concerns have been raised regarding growth in children. The correct implementation of these diets requires a multidisciplinary approach by highly specialized healthcare professionals, who will address the medical, social, and psychological concerns that a restrictive diet entails. Large-scale and long-term studies are needed to provide more robust data before carbohydrate restriction can be widely applied to patients with T1DM. Full article

The intestine is an important segment of the gastrointestinal tract, which is involved in complex processes that maintain the body’s normal homeostasis. It hosts a vast, diverse, and dynamic microbial community called the gut microbiota, which develops from birth. It has been observed that the gut microbiota is involved in essential physiological processes, including the development of the central nervous system via the gut microbiota–brain axis. An alteration of the gut microbiota can lead to serious health problems, including defective neurodevelopment. Thus, this paper aims to highlight the most recent advances in studies that focus on the link between the gut microbiota and the evolution of neurodevelopmental diseases in children. Currently, studies show that the use of drugs that stimulate and restore the gut microbiota (e.g., probiotics and prebiotics) have the potential to alleviate some of the symptoms associated with conditions such as Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder, Tic Disorder, Tourette Syndrome, epilepsy, and Down Syndrome. In addition, due to the challenges associated with drug administration in children, as well as the widespread shortage of medications intended for pediatric use, researchers are working on the development of new delivery systems. Liposome-based systems or solid lipid nanoparticles have been safely used for drug delivery in various pediatric conditions, which may also indicate their potential for use in the administration of microbiota-modulating therapies. Full article

Background: Developmental epileptic encephalopathies (DEEs) are often associated with variably severe cognitive and motor impairment and frequent refractory epilepsy, with many children not achieving adequate seizure control via standard antiepileptic medications. The classic ketogenic diet (KD) has proven effective in reducing seizure frequency and/or severity in a category of DEEs and in certain refractory epilepsies of infancy. However, its multifaceted mechanisms, e.g., epigenetic modulation, anti-inflammatory and antioxidative effects, and direct neuronal excitability changes, are balanced by a high burden and low long-term adherence. Medium-chain triglycerides (MCTs), particularly decanoic acid (C10:0), have gained attention in recent years for their potential direct inhibitory action on AMPA receptors, contributing to seizure reduction. Methods: A systematic review was conducted, including articles from January 2000 to January 2025, to explore the potential role of medium-chain triglyceride (MCT) add-on to classic KD and as MCT supplementation in free diets in the management of pediatric drug-resistant epilepsy (DRE). Results: Selected studies show how the action of MCTs, and decanoic acid in particular, is via negative modulation of AMPA receptors, with a positive impact on epileptic seizures. Conclusions: This review discusses the complexities of implementing and sustaining KD in children and presents recent pre-clinical and clinical evidence, including trials where MCTs (often enriched in decanoic acid) serve as an add-on therapy in both ketogenic and free/unrestricted diets. The summarized findings reinforce the therapeutic potential of MCTs, highlighting both the beneficial seizure outcomes and the hurdles that remain to be addressed through future research. Full article

Background/Objectives: Excessive screen exposure that negatively impacts a person’s life is referred to as problematic media use (PMU). In healthy children, PMU is associated with a sedentary lifestyle and negative health outcomes. However, this issue is not well understood in children with cerebral palsy (CP). The aim of our study was to evaluate PMU and screen exposure times in children with CP. Methods: All CP patients with variable etiology who were followed up at the child neurology clinic and met the inclusion criteria were included in our study. A total of 91 patients diagnosed with CP and 92 control children, aged 4–11, participated in the study. Daily screen exposure times, sleep durations, and body mass index (BMI) were evaluated. In children with CP, additional data such as the need for special education, CP subtype, epilepsy status, and mobility status were recorded. All participants were administered the long form of the Problematic Media Use Scale, which is valid for children aged 4–11. Results: When comparing screen exposure between the patient group and the control group, the patient group had significantly higher screen exposure (p < 0.001). Spearman’s rho correlation coefficients, calculated to evaluate the relationship between age, sleep duration, screen exposure time and screen addiction questionnaire scores of the children in the patient and control groups, were statistically significant. For the patient group specifically, there was a significant positive relationship between screen exposure duration and screen addiction questionnaire scores (r = 0.380, p < 0.001). Conclusions: In our study, it was seen that problematic media use was no different in CP patients within the same age group. However, screen exposure durations were found to be higher than in the normal population. Full article

Epilepsy is a prevalent neurological condition, having a wide range of phenotypic traits, which complicate the diagnosis process. Next-generation sequencing (NGS) techniques have improved the diagnostics for unexplained epilepsies. Our goal was to evaluate the utility and impact of genetic testing in the clinical management of pediatric epilepsies. In addition, we aimed to identify clinical factors that could predict a genetic diagnosis. This was a retrospective study of 140 pediatric patients with epilepsy with or without other neurological conditions that underwent NGS testing (multigene panel, WES = whole exome sequencing and/or WGS = whole genome sequencing). A comparison between genetically diagnosed versus non-diagnosed children was performed based on different clinical features. Univariate and multivariate logistic regression analysis was performed to identify clinical predictors of a positive genetic diagnosis. Most children underwent gene panel testing, while 30 had exome sequencing and 3 had genome sequencing. The overall diagnostic yield of genetic testing was 28.6% (40/140) for more than 28 genes. The most frequently identified genes with causative variants were SCN1A (n = 4), SCN2A (n = 3), STXBP1 (n = 3), MECP2 (n = 2), KCNQ2 (n = 2), PRRT2 (n = 2), and NEXMIF (n = 2). Significant predictors from the logistic regression model were a younger age at seizure onset (p = 0.015), the presence of intellectual disability (p = 0.021), and facial dysmorphism (p = 0.049). A genetic diagnosis led to an impact on the choice or duration of medication in 85% (34/40) of the children, as well as the recommendation for screening of comorbidities or multidisciplinary referrals in 45% (18/40) of children. Epilepsy is a highly heterogeneous disorder, both genetically and phenotypically. Less than one third of patients had a genetic diagnosis identified using panels, exomes, and/or genomes. An early onset and syndromic features (including global developmental delay) were more likely to receive a diagnosis and benefit from optimized disease management. Full article