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Aim Method Results Interpretation To evaluate a group of children with epilepsy and motor speech regression, with the aim of characterizing their speech disorders, electrographic features, and outcomes.Children referred to a tertiary developmental epilepsy clinic with epilepsy and motor speech regression were identified retrospectively. A clinical history was taken, and longitudinal speech and cognitive data were recorded. Speech samples were scored for severity and speech features. Seizure frequency and epileptiform discharges in the interictal electroencephalogram were analysed.Eighteen children (10 female) were evaluated, including seven with Landau–Kleffner syndrome and six with Rasmussen syndrome. Speech regression occurred at a mean age of 5 years (SD = 2 years 6 months), which was concurrent with seizure onset or peak seizure burden in eight children. Speech features included dysarthria (n = 13), phonological errors (n = 7), and dyspraxia (n = 6). Electrographic abnormalities occurred most frequently in the left centrotemporal and right frontal regions. Among children who were followed up, intelligibility of speech was affected in 13 at baseline and seven at follow‐up (p = 0.03). Expressive language standardized scores increased from a mean (SD) of 50.0 (11.3) to 91.4 (27.8) in children with Landau–Kleffner syndrome (mean change = 41.4, 95% confidence interval [CI] 0.04–82.8, p = 0.0498) and decreased from 75.2 (15.3) to 59.0 (9.8) in children with Rasmussen syndrome (mean change −16.2, 95% CI −9.0 to −23.4, p = 0.002) over the follow‐up.Motor speech disorders in epilepsy were severe, multifarious, and often fluctuated with seizure burden. Symptoms typically improved, especially in children with Landau–Kleffner syndrome, but rarely fully resolved. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance We aimed to investigate sleep in children with drug‐resistant epilepsy (DRE), including developmental and epileptic encephalopathies (DEEs). Next, we examined differences in sleep macrostructure and microstructure and questionnaire outcomes between children with well‐controlled epilepsy (WCE) and children with DRE. Furthermore, we wanted to identify factors associated with poor sleep outcome in these children, as some factors might be targets to improve epilepsy and neurodevelopmental outcomes.A cross‐sectional study was conducted in children 4 to 18‐years‐old. Children without epilepsy, with WCE, and with DRE were included. Overnight electroencephalography (EEG), including chin electromyography and electrooculography, to allow sleep staging, was performed. Parents were asked to fill out a sleep questionnaire. Classical five‐stage sleep scoring was performed manually, spindles were automatically counted, and slow wave activity (SWA) in the first and last hour of slow wave sleep was calculated.One hundred eighty‐two patients were included: 48 without epilepsy, 75 with WCE, and 59 with DRE. We found that children with DRE have significantly lower sleep efficiency (SE%), less time spent in rapid eye movement (REM) sleep, fewer sleep spindles, and a lower SWA decline over the night compared to children with WCE. Subjectively more severe sleep problems were reported by the caregivers and more daytime sleepiness was present in children with DRE. Least absolute shrinkage and selection operator (LASSO) regression showed that multifocal interictal epileptiform discharges (IEDs), benzodiazepine treatment, and longer duration of epilepsy were associated with lower SE% and lower REM sleep time. The presence of multifocal discharges and cerebral palsy was associated with fewer spindles. Benzodiazepine treatment, drug resistance, seizures during sleep, intellectual disability, and older age were associated with lower SWA decline.Both sleep macrostructure and microstructure are severely impacted in children with DRE, including those with DEEs. Epilepsy parameters play a distinct role in the disruption REM sleep, spindle count, and SWA decline. [ABSTRACT FROM AUTHOR]

Somatic mosaicism in a fraction of brain cells causes neurodevelopmental disorders, including childhood intractable epilepsy. However, the threshold for somatic mosaicism leading to brain dysfunction is unknown. In this study, we induced various mosaic burdens in focal cortical dysplasia type II (FCD II) mice, featuring mTOR somatic mosaicism and spontaneous behavioural seizures. The mosaic burdens ranged from approximately 1000 to 40 000 neurons expressing the mTOR mutant in the somatosensory or medial prefrontal cortex. Surprisingly, approximately 8000–9000 neurons expressing the MTOR mutant, extrapolated to constitute 0.08%–0.09% of total cells or roughly 0.04% of variant allele frequency in the mouse hemicortex, were sufficient to trigger epileptic seizures. The mutational burden was correlated with seizure frequency and onset, with a higher tendency for electrographic inter-ictal spikes and beta- and gamma-frequency oscillations in FCD II mice exceeding the threshold. Moreover, mutation-negative FCD II patients in deep sequencing of their bulky brain tissues revealed somatic mosaicism of the mTOR pathway genes as low as 0.07% in resected brain tissues through ultra-deep targeted sequencing (up to 20 million reads). Thus, our study suggests that extremely low levels of somatic mosaicism can contribute to brain dysfunction. [ABSTRACT FROM AUTHOR]

Blockade of Angiotensin type 1 receptor (AT1R) has potential therapeutic utility in the treatment of numerous detrimental consequences of epileptogenesis, including oxidative stress, neuroinflammation, and blood–brain barrier (BBB) dysfunction. We have recently shown that many of these pathological processes play a critical role in seizure onset and propagation in the Scn8a-N1768D mouse model. Here we investigate the efficacy and potential mechanism(s) of action of candesartan (CND), an FDA-approved angiotensin receptor blocker (ARB) indicated for hypertension, in improving outcomes in this model of pediatric epilepsy. We compared length of lifespan, seizure frequency, and BBB permeability in juvenile (D/D) and adult (D/+) mice treated with CND at times after seizure onset. We performed RNAseq on hippocampal tissue to quantify differences in genome-wide patterns of transcript abundance and inferred beneficial and detrimental effects of canonical pathways identified by enrichment methods in untreated and treated mice. Our results demonstrate that treatment with CND gives rise to increased survival, longer periods of seizure freedom, and diminished BBB permeability. CND treatment also partially reversed or ‘normalized’ disease-induced genome-wide gene expression profiles associated with inhibition of NF-κB, TNFα, IL-6, and TGF-β signaling in juvenile and adult mice. Pathway analyses reveal that efficacy of CND is due to its known dual mechanism of action as both an AT1R antagonist and a PPARγ agonist. The robust effectiveness of CND across ages, sexes and mouse strains is a positive indication for its translation to humans and its suitability of use for clinical trials in children with SCN8A epilepsy [ABSTRACT FROM AUTHOR]

Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL) is associated to BPTF gene haploinsufficiency. Epilepsy was not included in the initial descriptions of NEDDFL, but emerging evidence indicates that epileptic seizures occur in some affected individuals. This study aims to investigate the electroclinical epilepsy features in individuals with NEDDFL. We enrolled individuals with BPTF -related seizures or interictal epileptiform discharges (IEDs) on electroencephalography (EEG). Demographic, clinical, genetic, raw EEG, and neuroimaging data as well as response to antiseizure medication were assessed. We studied 11 individuals with a null variant in BPTF , including five previously unpublished ones. Median age at last observation was 9 years (range: 4 to 43 years). Eight individuals had epilepsy, one had a single unprovoked seizure, and two showed IEDs only. Key features included (1) early childhood epilepsy onset (median 4 years, range: 10 months to 7 years), (2) well-organized EEG background (all cases) and brief bursts of spikes and slow waves (50% of individuals), and (3) developmental delay preceding seizure onset. Spectrum of epilepsy severity varied from drug-resistant epilepsy (27%) to isolated IEDs without seizures (18%). Levetiracetam was widely used and reduced seizure frequency in 67% of the cases. Our study provides the first characterization of BPTF -related epilepsy. Early-childhood-onset epilepsy occurs in 19% of subjects, all presenting with a well-organized EEG background associated with generalized interictal epileptiform abnormalities in half of these cases. Drug resistance is rare. [ABSTRACT FROM AUTHOR]

Sleep is essential in the process of memory consolidation. Children and adolescents with epilepsy hold a significantly higher risk for memory impairment. Understanding the relationship between sleep and memory impairment in adolescents with epilepsy will help us to develop effective support services for this patient population. The present study provides a summary of the current research on the influence of epilepsy-related altered sleep patterns on memory consolidation in children and adolescents with epilepsy. The aim of this systematic review is to investigate the influence of epilepsy-related altered sleep conditions in children and adolescents and their impact on memory performance. A systematic review was conducted according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses using the search terms "memory," "sleep," "epilepsy," "children," and "adolescents." A total of 4 studies met the inclusion criteria. The review focused on the association of sleep disorders and memory performance in children and adolescents aged up to 21 years without psychiatric comorbidities. The reviewed studies highlight a higher risk of sleep disturbance and lower sleep quality in children with epilepsy in comparison to control groups. Group differences in memory consolidation were found before, but not after one night of sleep. Three studies reported a significant association between sleep and memory performance. Two studies demonstrated an association between nocturnal interictal epileptiform discharges and memory performance in adolescents. Children and adolescents with epilepsy have a higher risk of sleep and memory disorders. Nocturnal interictal epileptiform discharges have been shown to interfere with memory consolidation. Conclusions on underlying mechanisms remain unclear. Further case-control studies addressing sleep and its influence on memory problems in pediatric epilepsy patients are needed. [ABSTRACT FROM AUTHOR]

Approximately 10% to 20% of children with epilepsy experience status epilepticus (SE), and children with seizure clustering are at higher risk. Ketamine is growing in use for SE. This study examines the efficacy and safety of enteral ketamine in the treatment of convulsive status epilepticus (CSE) characterized by refractory seizure clusters and nonconvulsive status epilepticus (NCSE) in children with epilepsy. Patient charts were reviewed retrospectively. Children with epilepsy aged one to 21 years presenting in SE and treated with enteral ketamine between September 1, 2021 and September 1, 2022 at a pediatric tertiary care center were identified. Resolution or reduction in seizure frequency within 48 hours, clinical presentation, endotracheal intubation, hospitalization duration, side effects, and readmission were assessed. Nine patients aged two to 21 years were identified. Six patients presented in CSE characterized by recurrent seizures, and three patients presented in NCSE. Five patients had genetic epilepsies, including PCDH19- and MECP2-related epilepsy. Seven patients had resolution or reduction in seizures within 48 hours of ketamine initiation. Two patients were intubated. Hospitalization duration ranged from one to 34 days. Three patients reported side effects. Three patient readmissions with early ketamine treatment had equal or shorter hospitalizations. Enteral ketamine may prove an effective, well-tolerated option for treatment of convulsive and nonconvulsive SE in children with epilepsy, including genetic epilepsies, and may prevent intubation and shorten hospitalization time. [ABSTRACT FROM AUTHOR]

Background: Childhood epilepsies are caused by heterogeneous underlying disorders where approximately 40% of the origins of epilepsy can be attributed to genetic factors. The application of next-generation sequencing (NGS) has revolutionized molecular diagnostics and has enabled the identification of disease-causing genes and variants in childhood epilepsies. The objective of this study was to use NGS to identify variants in patients with childhood epilepsy, to expand the variant spectrum and discover potential therapeutic targets. Methods: In our study, 55 children with epilepsy of unknown etiology were analyzed by combining clinical-exome and whole-exome sequencing. Novel variants were characterized using various in silico algorithms for pathogenicity and structure prediction. Results: The molecular genetic cause of epilepsy was identified in 28 patients and the overall diagnostic success rate was 50.9%. We identified variants in 22 different genes associated with epilepsy that correlate well with the described phenotype. SCN1A gene variants were found in five unrelated patients, while ALDH7A1 and KCNQ2 gene variants were found twice. In the other 19 genes, variants were found only in a single patient. This includes genes such as ASH1L, CSNK2B, RHOBTB2, and SLC13A5, which have only recently been associated with epilepsy. Almost half of diagnosed patients (46.4%) carried novel variants. Interestingly, we identified variants in ALDH7A1, KCNQ2, PNPO, SCN1A, and SCN2A resulting in gene-directed therapy decisions for 11 children from our study, including four children who all carried novel SCN1A genetic variants. Conclusions: Described novel variants will contribute to a better understanding of the European genetic landscape, while insights into the genotype-phenotype correlation will contribute to a better understanding of childhood epilepsies worldwide. Given the expansion of molecular-based approaches, each newly identified genetic variant could become a potential therapeutic target. [ABSTRACT FROM AUTHOR]

• Alterations in local cortical morphology and individual-based morphological brain networks were studied in Rolandic epilepsy (RE). • The RE group had disrupted morphological network organization beyond local morphology changes. • Abnormal morphological brain network alterations may provide new theoretical basis for exploring neuropathological mechanisms in RE. To investigate the local cortical morphology and individual-based morphological brain networks (MBNs) changes in children with Rolandic epilepsy (RE). Based on the structural MRI data of 56 children with RE and 56 healthy controls (HC), we constructed four types of individual-based MBNs using morphological indices (cortical thickness [CT], fractal dimension [FD], gyrification index [GI], and sulcal depth [SD]). The global and nodal properties of the brain networks were analyzed using graph theory. The between-group difference in local morphology and network topology was estimated, and partial correlation analysis was further analyzed. Compared with the HC, children with RE showed regional GI increases in the right posterior cingulate gyrus and SD increases in the right anterior cingulate gyrus and medial prefrontal cortex. Regarding the network level, RE exhibited increased characteristic path length in CT-based and FD-based networks, while decreased FD-based network node efficiency in the right inferior frontal gyrus. No significant correlation between altered morphological features and clinical variables was found in RE. These findings indicated that children with RE have disrupted morphological brain network organization beyond local morphology changes. The present study could provide more theoretical basis for exploring the neuropathological mechanisms in RE. [ABSTRACT FROM AUTHOR]

To evaluate the risk of epilepsy in children who received neonatal phototherapy. A cohort of live singletons born at a Danish hospital (2002–2016) with a gestational age ≥ 35 weeks. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of epilepsy in children treated with neonatal phototherapy compared to children not treated with neonatal phototherapy in the general population, and in a subpopulation of children who had serum bilirubin measurement. Adjusted HRs (aHR) were computed using multivariable and propensity score matching models to take maternal and neonatal factors into consideration. Children were followed from day 29 after birth to diagnosis of epilepsy, death, emigration, or December 31, 2016. Among 65,365 children, 958 (1.5%) received neonatal phototherapy. Seven children (incidence rates (IRs): 10.8 /10,000 person-years) who received neonatal phototherapy and 354 children (IR: 7.7) who did not receive neonatal phototherapy were diagnosed with epilepsy. Neonatal phototherapy was not associated with an increased risk of epilepsy using the multivariable (aHR 0.95, 95% CI: 0.43–2.09) and propensity score matched (aHR 0.94, 95% CI: 0.39–2.28) models. In the subpopulation of 9,378 children with bilirubin measurement, 928 (9.9%) received neonatal phototherapy. In the analysis of the subpopulation in which bilirubin level and age at the time of bilirubin measurement were further taking into consideration, neonatal phototherapy was not associated with an increased risk of epilepsy using the multivariable (aHR 1.26, 95% CI: 0.54–2.97) and propensity score matched (aHR 1.24, 95% CI: 0.47–3.25) models, Conclusions: Neonatal phototherapy was not associated with an increased risk of epilepsy after taking maternal and neonatal factors into consideration. What is known: • A few studies have suggested that neonatal phototherapy for hyperbilirubinemia may increase the risk of childhood epilepsy. • Whether the observed associations contribute to hyperbilirubinemia, phototherapy, or underlying factors requires further investigation. What is new: • This study revealed no increased risk of epilepsy in children treated with neonatal phototherapy compared to children not treated with phototherapy after taking maternal and neonatal factors into consideration. • After further taking bilirubin level and age at the time of bilirubin measurement into consideration, neonatal phototherapy was not associated with an increased risk of epilepsy. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate the diagnostic and prognostic role of cerebrospinal fluid (CSF) biomarkers in the diagnostic work-up of glucose transporter 1 (GLUT1) deficiency. Reported here is a systematic review according to PRISMA guidelines collecting clinical and biochemical data about all published patients who underwent CSF analysis. Clinical phenotypes were compared between groups defined by the levels of CSF glucose (≤ 2.2 mmol/L versus > 2.2 mmol/L), CSF/blood glucose ratio (≤ 0.45 versus > 0.45), and CSF lactate (≤ 1 mmol/L versus > 1 mmol/L). Five hundred sixty-two patients fulfilled the inclusion criteria with a mean age at the diagnosis of 8.6 ± 6.7 years. Patients with CSF glucose ≤ 2.2 mmol/L and CSF/blood glucose ratio ≤ 0.45 presented with an earlier onset of symptoms (16.4 ± 22.0 versus 54.4 ± 45.9 months, p < 0.01; 15.7 ± 23.8 versus 40.9 ± 38.0 months, p < 0.01) and received an earlier molecular genetic confirmation (92.1 ± 72.8 versus 157.1 ± 106.2 months, p < 0.01). CSF glucose ≤ 2.2 mmol/L was consistently associated with response to ketogenic diet (p = 0.018) and antiseizure medications (p = 0.025). CSF/blood glucose ratio ≤ 0.45 was significantly associated with absence seizures (p = 0.048), paroxysmal exercise‐induced dyskinesia (p = 0.046), and intellectual disability (p = 0.016) while CSF lactate > 1 mmol/L was associated with a response to antiseizure medications (p = 0.026) but not to ketogenic diet. Conclusions:This systematic review supported the diagnostic usefulness of lumbar puncture for the early identification of patients with GLUT1 deficiency responsive to treatments especially if they present with co-occurring epilepsy, movement, and neurodevelopmental disorders. What is Known: • Phenotypes of GLUT1 deficiency syndrome range between early epileptic and developmental encephalopathy to paroxysmal movement disorders and developmental impairment What is New: • CSF blood/glucose ratio may predict better than CSF glucose the diagnosis in children presenting with early onset absences • CSF blood/glucose ratio may predict better than CSF glucose the diagnosis in children presenting with paroxysmal exercise induced dyskinesia and intellectual disability. • CSF glucose may predict better than CSF blood/glucose and lactate the response to ketogenic diet and antiseizure medications. [ABSTRACT FROM AUTHOR]

Duplications in chromosomal locus 2q24.3 region that solely involve SCN2A remain less explored. Favorable outcomes have been reported in patients with SCN2A gene duplications in cases of mild epilepsy with onset during the neonatal to infantile period, or in infantile epileptic spasm syndrome. Herein, we report a case of microduplications, including SCN2A gene duplications, wherein developmental/epileptic encephalopathy with spike-wave activation during sleep (D/EE-SWAS) developed. A 3-day-old girl without birth complications exhibited tonic seizures in her right limb with eye deviation to the right. She developed drug-resistant seizures, including atypical absence seizures, at 1 year and 6 months old. Despite achieving seizure freedom at 9 years old, she experienced academic difficulties. D/EE-SWAS was diagnosed based on the long-term electroencephalogram findings. Following a corpus callosotomy at 11 years old, her academic performance and emotional expression improved. Comprehensive genetic analysis at 10 years old revealed a microduplication spanning approximately 300 kb within the 2q24.3 region, which included a segment of the SCN2A gene and an adjacent CSRNP3 gene. In conclusion, we reported a rare case of duplications solely encompassing SCN2A. Corpus callosotomy resolved the D/EE-SWAS. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance To assess whether children with febrile seizures and/or epilepsy were at increased risk of experiencing internalizing symptoms or psychotic‐like experiences at age 11 years.This cohort study includes 44 819 children from the 11‐year follow up of the Danish National Birth Cohort. Information on childhood seizures was retrieved from the Danish National Patient Registry, whereas child psychiatric symptoms were assessed in a web‐based questionnaire using the Adolescent Psychotic‐like Symptom Screener and the Strength and Difficulties Questionnaire. Adjusted odds ratios (aORs) with corresponding 95% confidence intervals (CIs) for the association between childhood seizures and internalizing symptoms (symptom score ≥8) and psychotic‐like experiences (≥2 definite experiences) were obtained using logistic regression models.A total of 1620 children with febrile seizures (3.6%), and 311 children with epilepsy (0.7%) were identified. When adjusted for potential confounders, no association between febrile seizures and psychiatric symptoms was observed, and no association was observed between epilepsy and psychotic‐like experiences. However, the OR for internalizing symptoms was 1.76 (95% CI: 1.20–2.58) in children with epilepsy compared to children without. This higher risk was evident mainly in boys (OR 2.30, 95% CI 1.37–3.85), children with ≥2 epilepsy‐related hospital admissions (OR 2.79, 95% CI 1.81–4.32), and children whose age at first epilepsy‐related hospital admission was 0–3 years (OR 2.47, 95% CI 1.45–4.19).No association was found between febrile seizures and psychiatric symptoms or epilepsy and psychotic‐like experiences at age 11. However, boys with epilepsy were at higher risk of experiencing internalizing symptoms. [ABSTRACT FROM AUTHOR]

Objective: Epilepsy-related stigma is a global problem, yet there has been an inadequate focus on children and adolescents. The purpose of this study was to determine the status quo of stigma and its determinants among children and adolescents with epilepsy in China. Methods: A multicenter cross-sectional study was conducted across nine hospitals in eight cities within six provinces in China from 10 October 2023 to 15 June 2024. Participants included patients aged 8 to 18 years with epilepsy and their caregivers. Felt stigma was assessed with the Kilifi Stigma Scale for Epilepsy (KSSE). Social support and self-efficacy were collected through the Social Support Rating Scale (SSRS) and the Generalized Self-Efficacy Scale (GSES). The data were analyzed using t-tests, analysis of variance (ANOVA), Spearman correlation analysis, and multiple linear regression analysis. Results: The study enrolled 281 children and adolescents, with a mean age of 12.25 years (SD = 2.56), including 46.6% females. A total of 35.6% participants had self-reported felt stigma. The mean KSSE score is 9.58 (SD = 7.11). Meanwhile, stigma scores correlated strongly with reduced social support (r=-0.55, p<0.01) and self-efficacy (r=-0.43, p<0.01). Place of residence (rural vs. non-rural), academic performance (average and above vs. fair or poor), region (western region vs. non-western region), duration of epilepsy (<5 years vs. >5years), drug-resistant epilepsy (yes vs. no), comorbidities (yes vs. no), social support and self-efficacy are major influencing factors among the complex factors influencing the felt stigma among children and adolescents. Conclusion: Medical staff should be more aware of stigma among children and adolescents with epilepsy, especially those who live in rural and western areas, have poor academic performance, have epilepsy duration of more than 5 years, have drug-resistant epilepsy, and have comorbidities, who are at higher risk of stigma. It is recommended that effective measures be taken to alleviate stigma by improving children and adolescents' self-efficacy and providing more social support for them and their families. [ABSTRACT FROM AUTHOR]

Epilepsy is one of the most common neurological disorders in children. Diagnosing epilepsy in children can be very challenging, especially as it often coexists with neurodevelopmental conditions like autism and ADHD. Functional brain networks obtained from neuroimaging and electrophysiological data in wakefulness and sleep have been shown to contain signatures of neurological disorders, and can potentially support the diagnosis and management of co-occurring neurodevelopmental conditions. In this work, we use electroencephalography (EEG) recordings from children, in restful wakefulness and sleep, to extract functional connectivity networks in different frequency bands. We explore the relationship of these networks with epilepsy diagnosis and with measures of neurodevelopmental traits, obtained from questionnaires used as screening tools for autism and ADHD. We explore differences in network markers between children with and without epilepsy in wake and sleep, and quantify the correlation between such markers and measures of neurodevelopmental traits. Our findings highlight the importance of considering the interplay between epilepsy and neurodevelopmental traits when exploring network markers of epilepsy. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Ketogenic diet therapy (KDT) has been recommended as a treatment for drug‐resistant epilepsy in children and young people since 2012 in the National Institute for Health and Care Excellence Clinical Guidelines for Epilepsies. The Ketogenic Dietitians Research Network completed a survey in 2017 to assess the impact of these guidelines.An online survey was circulated to ketogenic dietitians across the UK and Ireland. The results were compared with those of the 2017 survey.The number of individuals following KDT was 854, comprising an increase of 13% since 2017. Service sizes ranged widely, with 1–74 (median 16) patients on the diet. Of 36 services, 30 had a waiting list, ranging from 2 to 67 (median 9) patients. The classical diet continued to be the most common KDT used (58% of patients). Ten services reported use of a new flexible medium chain triglyceride protocol. Some 48% of patients (n = 427) had been following the KDT for over 2 years, comprising an 18% increase since 2017. Of these, 68 (15.9%) had attempted to wean off KDT but had to re‐start as a result of a deterioration in seizures.The number of individuals following medical KDT remains stable. Referral numbers and waiting lists remain high, highlighting that KDT is still a well‐recognised treatment option for drug‐resistant epilepsy. The types of KDT used are similar to previous years, although increasingly flexible protocols are being adopted. Longer‐term use of KDT is increasing, with a proportion of patients requiring long‐term use to maintain seizure control. [ABSTRACT FROM AUTHOR]

Background: Self-limited focal epilepsies of childhood, including self-limited epilepsy with centrotemporal spikes (SeLECTS), idiopathic childhood occipital epilepsy of Gastaut (ICOE-G), and self-limited epilepsy with autonomic seizures (SeLEAS), were considered benign conditions. However, recent research assumed potential adverse impacts on sleep, cognition, behavior, and emotional well-being. Our aim was to investigate the effects of self-limited focal epilepsies on sleep architecture, cognitive functions, behavior, and emotional disturbances in drug naive children. A cross-sectional study was conducted on 46 newly diagnosed children (ages 6–12) with SeLECTS (n = 22), ICOE-G (n = 12), SeLEAS (n = 12), and 20 healthy controls. Overnight polysomnography was performed. Cognitive assessments included intelligence scales, executive function tests, verbal fluency, visuospatial abilities, and memory. Behavioral and emotional problems were evaluated using standardized questionnaires and psychiatric interviews. Results: Children with epilepsy exhibited significant disturbances in sleep architecture, impairments in cognitive domains (executive functions, verbal fluency, visuospatial skills, and memory), and higher rates of internalizing/externalizing problems, social issues, attention deficit hyperactive disorder, depression, and anxiety compared to controls. No significant differences were found among the three epilepsy subtypes. Conclusion: Self-limited focal epilepsies in childhood are associated with sleep disruption, cognitive deficits, behavioral issues, and psychiatric comorbidities, challenging their traditional "benign" perception. Comprehensive management approaches addressing these multidimensional impacts are warranted. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance Previous studies assessing factors associated with drug‐resistant epilepsy (DRE) were constrained by their amalgamation of all epilepsy syndromes in their analyses and the absence of uniform criteria for defining DRE. Our objective was to identify predictors of DRE among the four primary childhood epilepsy syndrome groups within a cohort of children with new onset seizures, using the International League Against Epilepsy (ILAE) definition of DRE and the recent classification of epilepsies.This is a prospective study of 676 children with new onset seizures initiated on antiseizure medication. Patients were monitored for the occurrence of DRE according to the ILAE criteria and were categorized into one of four epilepsy groups: self‐limited focal epilepsies (SeLFEs), genetic generalized epilepsies (GGEs), developmental epileptic encephalopathies (DEEs), and focal epilepsies. Cox regression analysis was performed to identify predictors of DRE within each epilepsy group.Overall, 29.3% of children were classified as having DRE, with the highest incidence observed among children diagnosed with DEEs (77.7%), followed by focal epilepsies (31.5%). Across the entire cohort, predictors of DRE included the presence of an epileptogenic lesion, a higher pretreatment number of seizures, experiencing multiple seizure types, presence and severity of intellectual and developmental delay, myoclonus, and younger age at epilepsy onset. Within the GGEs, only a younger age at seizure onset and experiencing multiple seizure types predicted DRE. Among focal epilepsies, predictors of DRE included the presence of an epileptogenic lesion, experiencing multiple seizure types, and having a greater number of pretreatment seizures. Within the DEEs, predictors of DRE were the occurrence of tonic seizures. Predictors of DRE within SeLFEs could not be identified.This study indicates that different epilepsy syndromes are associated with distinct predictors of drug resistance. Anticipation of drug resistance within various groups is feasible using accessible clinical variables throughout the disease course. [ABSTRACT FROM AUTHOR]

Aim To determine changes in the quality of life associated with epilepsy in school-age children with newly diagnosed uncomplicated epilepsy over the first six months after diagnosis to find points relevant for the early prevention of deterioration in quality of life. Methods This prospective follow-up study, performed in University Children’s Hospital in Belgrade, enrolled 60 school-aged children with recently diagnosed epilepsy, along with their parents. The respondents completed the Children with Epilepsy Quality of Life immediately following the diagnosis of epilepsy and six months later. Results Significant decline was observed in the domains related to intrapersonal/emotional relationships by both children (P<0.001) and their parents (P=0.03), and in the need to keep epilepsy a secret as observed by parents (P=0.04). Significant improvement was found in the Interpersonal/Social domain as rated by parents (P=0.001). Total quality-of-life scores, as assessed by children and parents, did not change significantly. Conclusion Bearing in mind that stigma and intrapersonal struggles are the major factors affecting the quality of life in children with epilepsy, psychological and social support is highly recommended in the first six months following an epilepsy diagnosis. Since intrapersonal relationships improved over six months, compensating for other deteriorations in the quality of life, children with epilepsy should be encouraged to socialize with their peers and to join organizations and actions that encourage social contact. [ABSTRACT FROM AUTHOR]

This document is a summary of a special issue of the journal Brain Sciences on recent advances in the pathophysiology and therapeutic approaches in epilepsy. The document highlights the global impact of epilepsy, with over 65 million people affected worldwide. It emphasizes the need for a deeper understanding of the biochemical, structural, physiological, and molecular changes in epileptic brains to develop novel therapeutic targets and treatment options. The special issue includes twelve papers, including research articles, review articles, and a systematic review, covering topics such as drug-resistant epilepsy, neuroinflammation, post-traumatic epilepsy, surgical treatments, status epilepticus, self-limited focal epilepsy, transition readiness, epilepsy networks, and interictal spikes. The articles aim to expand our understanding of epilepsy and contribute to the development of new treatment approaches. [Extracted from the article]

Genotype and clinical phenotype analyses of 128 children were performed based on whole exome sequencing (WES), providing a reference for the provision of genetic counseling and the precise diagnosis and treatment of epilepsy. A total of 128 children with unexplained epilepsy were included in this study, and all their clinical data were analyzed. The children's treatments, epilepsy control, and neurodevelopmental levels were regularly followed up every 3 months. The genetic diagnostic yield of the 128 children with epilepsy is 50.8%, with an SNV diagnostic yield of 39.8% and a CNV diagnostic yield of 12.5%. Among the 128 children with epilepsy, 57.0% had onset of epilepsy in infancy, 25.8% have more than two clinical seizure forms, 62.5% require two or more anti‐epileptic drug treatments, and 72.7% of the children have varying degrees of psychomotor development retardation. There are significant differences between ages of onset, neurodevelopmental levels and the presence of drug resistance in the genetic diagnostic yield (all p < 0.05). The 52 pathogenic/likely pathogenic SNVs involve 31 genes, with genes encoding ion channels having the largest number of mutations (30.8%). There were 16 cases of pathogenic/possibly pathogenic CNVs, among which the main proportions of CNVs were located in chromosome 15 and chromosome 16. Trio‐WES is an essential tool for the genetic diagnosis of unexplained epilepsy, with a genetic diagnostic yield of up to 50.8%. Early genetic testing can provide an initiate appropriate therapies and accurate molecular diagnosis. [ABSTRACT FROM AUTHOR]

Background/Objectives: To determine the impact of psychiatric disorders on epilepsy treatment outcomes and healthcare utilization in children with epilepsy (CWE) based on the presence or timing of the onset of psychiatric disorders. Methods: This retrospective controlled study enrolled children (age < 18 years) with newly diagnosed epilepsy into four groups stratified by the presence and timing of the onset of psychiatric disorders (None: no psychiatric disorders; Before: psychiatric disorders only preceding the epilepsy diagnosis; After: new psychiatric disorders diagnosed only after the epilepsy diagnosis; Mixed: different psychiatric disorders diagnosed both before and after epilepsy diagnosis) and compared the intergroup differences in epilepsy treatment outcomes and healthcare utilization. Results: Among the CWE (n = 37,678), 13,285 (35.26%) had comorbid psychiatric disorders. The After (n = 7892), Mixed (n = 3105), and Before (n = 2288) groups had significantly longer treatment periods than those in the None group (p < 0.001). Compared with the None group, the remaining groups had significantly higher frequencies of outpatient visits, emergency room visits, and admissions and higher rates of status epilepticus and drug-resistant epilepsy (p < 0.001, respectively), with higher odds ratios [95% confidence interval] for status epilepticus (2.92 [2.68–3.18]) and drug-resistant epilepsy (3.01 [2.85–3.17]) in the After group. Conclusions: Psychiatric comorbidities, diagnosed before and after epilepsy diagnosis, negatively affected the treatment outcomes. CWE without prior psychiatric disorders that were newly diagnosed during epilepsy treatment had the worst outcomes and the highest healthcare utilization rates. [ABSTRACT FROM AUTHOR]

Aims: Vigabatrin is an antiepileptic drug used to treat some forms of severe epilepsy in children. The main adverse effect is ocular toxicity, which is related to the cumulative dose. The aim of the study is to identify an acceptable exposure range, both through the development of a population pharmacokinetic model of vigabatrin in children enabling us to calculate patient exposure and through the study of therapeutic response. Methods: We performed a retrospective study including children with epilepsy followed at Necker‐Enfants Malades hospital who had a vigabatrin assay between January 2019 and January 2022. The population pharmacokinetic study was performed on Monolix2021 using a nonlinear mixed‐effects modelling approach. Children treated for epileptic spasms were classified into responder and nonresponder groups according to whether the spasms resolved, in order to identify an effective plasma exposure range. Results: We included 79 patients and analysed 159 samples. The median age was 4.2 years (range 0.3–18). A 2‐compartment model with allometry and creatinine clearance on clearance best fit our data. Exposure analysis was performed on 61 patients with epileptic spasms. Of the 22 patients who responded (36%), 95% had an AUC0–24 between 264 and 549 mg.h.L−1. Conclusions: The population pharmacokinetic model allowed us to identify bodyweight and creatinine clearance as the 2 main factors explaining the observed interindividual variability of vigabatrin. An acceptable exposure range was defined in this study. A target concentration intervention approach using this pharmacokinetic model could be used to avoid overexposure in responder patients. [ABSTRACT FROM AUTHOR]

Population-based data on drug-resistant epilepsy (DRE) are lacking. This retrospective study aimed to determine the prevalence and incidence of pediatric epilepsy and DRE in South Korea using health insurance claims data from the Health Insurance Review and Assessment Service (2013–2022). Epilepsy and DRE prevalence and incidence in children <18 years old were estimated over time and by age and sex. Results showed that the age-standardized prevalence and incidence rates of epilepsy increased. The age-standardized prevalence rate of DRE increased, while the age-standardized incidence rate remained unchanged. The standardized prevalence rate of DRE was 0.26 per 1000 persons, and the average standardized incidence rate of DRE was 0.06 per 1000 persons. The prevalence rate of DRE gradually increased with age, with age 0 demonstrating the highest incidence rate. The prevalence of generalized DRE was the highest across all ages, and incidence was the highest at 0 years. Conversely, the incidence of focal DRE did not change with age. Our study revealed a stable incidence rate of DRE in Korea, despite increased prevalence. DRE incidence was the highest in the first year of life, with the generalized type being the most prevalent. [ABSTRACT FROM AUTHOR]

Outcomes following vagus nerve stimulation (VNS) improve over years after implantation in children with drug‐resistant epilepsy. The added value of deep brain stimulation (DBS) instead of continued VNS optimization is unknown. In a prospective, non‐blinded, randomized patient preference trial of 18 children (aged 8–17 years) who did not respond to VNS after at least 1 year, add‐on DBS resulted in greater seizure reduction compared with an additional year of VNS optimization (51.9% vs. 12.3%, p = 0.047). Add‐on DBS also resulted in less bothersome seizures (p = 0.03), but no change in quality of life. DBS may be considered earlier for childhood epilepsy after non‐response to VNS. ANN NEUROL 2024;96:405–411 [ABSTRACT FROM AUTHOR]

Introduction: Stereoelectroencephalography (SEEG) is valuable for delineating the seizure onset zone (SOZ) in pharmacoresistant epilepsy when non-invasive presurgical techniques are inconclusive. Secondary epilepsy surgery after initial failure is challenging and there is limited research on SEEG following failed epilepsy surgery in children. Objective: The objective of this manuscript is to present the outcomes of children who underwent SEEG after failed epilepsy surgery. Methods: In this single-institution retrospective study, demographics, previous surgery data, SEEG characteristics, management, and follow-up were analyzed for pediatric patients who underwent SEEG after unsuccessful epilepsy surgery between August 2016 and February 2023. Results: Fifty three patients underwent SEEG investigation during this period. Of this, 13 patients were identified who had unsuccessful initial epilepsy surgery (24%). Of these 13 patients, six patients (46%) experienced unsuccessful resective epilepsy surgery that targeted the temporal lobe, six patients (46%) underwent surgery involving the frontal lobe, and one patient (8%) had laser interstitial thermal therapy (LITT) of the right insula. SEEG in two thirds of patients (4/6) with initial failed temporal resections revealed expanded SOZ to include the insula. All 13 patients (100%) had a subsequent surgery after SEEG which was either LITT (54%) or surgical resection (46%). After the subsequent surgery, a favorable outcome (Engel class I/II) was achieved by eight patients (62%), while five patients experienced an unfavorable outcome (Engel class III/IV, 38%). Of the six patients with secondary surgical resection, four patients (67%) had favorable outcomes, while of the seven patients with LITT, two patients (29%) had favorable outcomes (Engel I/II). Average follow-up after the subsequent surgery was 37 months ±23 months. Conclusion: SEEG following initial failed resective epilepsy surgery may help guide next steps at identifying residual epileptogenic cortex and is associated with favorable seizure control outcomes. [ABSTRACT FROM AUTHOR]

Background: Observational studies have indicated that psychiatric disorders are the most common comorbidities in pediatric epilepsy. However, the existence and direction of a causal relationship between the two remains controversial. This study aims to investigate the association between common childhood psychiatric disorders and epilepsy using a two-sample, bidirectional Mendelian randomization (MR) approach. Methods: Genetic instruments were obtained from the most recent and largest genome-wide association studies (GWAS), including datasets for epilepsy (N_case = 29,994, N_control = 52,538), attention deficit hyperactivity disorder (ADHD) (N_case = 38,691, N_control = 186,843), autism spectrum disorder (ASD) (N_case = 18,381, N_control = 27,969), and Tourette syndrome (TS) (N_case = 4,819, N_control = 9488). MR analyses were conducted using the inverse variance weighted (IVW) method, weighted median method, and MR-Egger regression. Results: No reliable evidence was found to suggest a causal effect of ADHD, ASD, or TS on epilepsy, nor was there any reliable evidence indicating that epilepsy increases the risk of these three psychiatric disorders. These findings remained consistent across various sensitivity analyses. Conclusion: Although observational studies have highlighted a high comorbidity rate between pediatric epilepsy and psychiatric disorders like ADHD and ASD, the MR analysis did not confirm a causal relationship between them. This suggests that previous studies might have been influenced by confounding biases or other biases, potentially overestimating the true relationship. A deeper understanding of the mechanisms underlying these comorbidities is crucial for refining the treatment of pediatric epilepsy. [ABSTRACT FROM AUTHOR]

Purpose: In brain development, Myelination is the characteristic feature of white matter maturation, which plays an important role in efficient information transmitting. The white matter abnormality has been reported to be associated with self-limited epilepsy with centrotemporal spikes (SeLECTS). This study aimed to detect the altered white matter region in the SeLECTS patients by the combination of diffusion tensor imaging (DTI) and quantitative susceptibility mapping (QSM) technique. Methods: 27 children with SeLECTS and 23 age- and gender-matched healthy children were enrolled. All participants were scanned with 3.0-T MRI to acquire the structure, diffusion and susceptibility-weighted data. The susceptibility and diffusion weighted data were processed to obtain quantitative susceptibility map and fraction anisotropy (FA) map. Then voxel-wise tract-based spatial statistics (TBSS) were used to analyze quantitative susceptibility and FA data. Results: Both DTI and QSM revealed extensive white matter alterations in the frontal, parietal, and temporal lobes in SeLECTS patients. The overlapped region of DTI and QSM analyses was located in the fiber tracts of the corona radiata. The FA values in this overlapped region were negatively correlated with the magnetic susceptibility values. Conclusion: Our results suggest that TBSS-based QSM can be employed as a novel approach for characterizing alterations in white matter in SeLECTS. And the combination of QSM and DTI can provide a more comprehensive evaluation of white matter integrity by utilizing different biophysical features. [ABSTRACT FROM AUTHOR]

Children with epilepsy are at increased risk for language and reading difficulties. Phonological processing and language underlie reading success, yet their association with reading achievement in children with epilepsy is unknown. We assessed phonological processing, oral language, and reading in children (ages 6 to 12) with epilepsy (EP; n = 6), language problems (LP; n = 14), and typical development (TD; n = 15). The EP and LP group had lower scores on all measures compared with the TD group, with the EP group scoring the lowest on reading comprehension. Phonological processing followed by epilepsy diagnosis predicted reading decoding. Language followed by epilepsy diagnosis predicted reading comprehension. Thus, reading problems in children with epilepsy are not fully explained by their phonological processing or language deficits. Further research that considers other cognitive processes important for reading (e.g., executive function) in this population may help inform our understanding of their reading success. We investigated differences in phonological processing, language, and reading in children with epilepsy compared with children with and without language problems. Results show that children with epilepsy have difficulty deciphering the sounds of language and that epilepsy is associated with difficulty sounding out words and comprehending written passages. The findings suggest that there may be other aspects of cognition that impact reading ability in children with epilepsy. [ABSTRACT FROM AUTHOR]

Objective: Corticosteroids and adrenocorticotropic hormone (ACTH) are the therapy of choice to treat infantile spasms. However, systematic studies about their use in other types of childhood epilepsies remain rare and ACTH can have serious side effects. This study compares the interictal epileptic activity (IEA) burden (% of electroencephalography (EEG) time with IEDs) in children with genetic drug‐resistant epilepsy before and after a standardized treatment with pulsatile corticoid therapy (PCT). Methods: Children with drug‐resistant epilepsy underwent a standardized protocol for PCT with cycles of high‐dose dexamethasone (20 mg/m2 body surface) intravenously. Patients were hospitalized for 3 days per PCT cycle and EEGs were obtained before initiation of treatment (baseline) and during the hospitalization around the time of every second cycle. EEG recordings during sleep and wakefulness were obtained. IEA burden was compared before and after PCT. Secondary outcome measures included the sleep spindle rate, the seizure frequency and subjective evaluation in a standardized interview. Results: In the cohort of 24 children (10 female, 6.2 ± 3.4 years), IEA burden was lower in the EEG after PCT compared to the baseline (baseline: 5.4% [0.7–97.3] vs. after PCT: 1.5% [0–96.9], p = 0.001, d = −0.41). Sleep physiology expressed by sleep spindles improved after PCT with enhanced fast spindle rates (0.8/min [0–2.2] vs. 1.5/min [0.2–3.4], p = 0.045, d = 0.36). Seizure frequency was decreased in 17 of the 24 patients (70.8%) with one patient achieving seizure freedom. The majority of patients improved in quality of life (79.2%), and sleep (81.3%). No serious adverse effects were documented. Significance: This study systematically assessed the effect of PCT in children with genetic / suspected genetic drug‐resistant epilepsy. PCT was found to not only reduce the IEA burden but also increase sleep spindle rates, which are important for cognitive functioning. Plain Language Summary: In this study, children with a form of epilepsy, which is resistant against antiseizure medication, received a systematic treatment with corticosteroids over multiple cycles in the hospital. It was found that not only the epileptic activity was reduced but also the sleep of the patients was improved after the treatment. These findings could provide the basis for extending the use of corticosteroids in children with epilepsy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prevalence of and risk factors for attention‐deficit/hyperactivity disorder (ADHD) in children with epilepsy (CWE). Methods: We conducted a systematic search in PubMed and Embase for the meta‐analysis. The pooled prevalence of ADHD was calculated using a random‐effects model; subgroup analyses were performed to explore heterogeneity. We collected raw data from articles reporting potential risk factors, which were included in the subsequent risk factor analysis. Results: Forty‐six articles met the inclusion criteria for the meta‐analysis, which showed a pooled ADHD prevalence of 30.7% in CWE, with a predominance of the inattentive subtype of ADHD; the heterogeneity of prevalence was related to population source/study setting (clinic based, community based, or database based) and method of ADHD diagnosis (with or without clinical review). Risk factors for ADHD in epilepsy included younger age, intellectual/developmental disabilities, a family history of epilepsy, earlier epilepsy onset, absence epilepsy, more frequent seizures, and polytherapy; In contrast, risk factors such as sex, generalized epilepsy or seizures, epilepsy etiology, and electroencephalogram abnormalities were not significantly associated with the occurrence of ADHD. Significance: The prevalence of ADHD in CWE is high and several potential risk factors are associated with it. This study contributes to a better understanding of ADHD in epilepsy for screening and treatment. Plain Language Summary: This systematic review summarizes the prevalence of attention‐deficit/hyperactivity disorder (ADHD) occurring in children with epilepsy and analyses the risk factors for comorbid ADHD in epilepsy. By reviewing 46 articles, we concluded that the overall prevalence of ADHD in children with epilepsy was 30.7% and that intellectual/developmental disabilities were the most significant risk factor for combined ADHD in children with epilepsy. This study provides a wealth of information on comorbid ADHD in epilepsy, which will help clinicians identify and treat potential ADHD in children with epilepsy in a timely manner. [ABSTRACT FROM AUTHOR]

Background: Micronutrient levels play a critical role in epilepsy. This study investigates the impact of micronutrient levels on epilepsy via Mendelian randomization (MR). Methods: A two-sample MR framework evaluated the genetic association between 15 serum micronutrients and epilepsy phenotypes. The analysis included calcium, iron, zinc, selenium, copper, magnesium, potassium, folate, vitamins B6, B12, C, D, E, retinol, and carotene against all epilepsy, generalized epilepsy, childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), generalized tonic-clonic seizures alone and with spike-wave electroencephalography (GTCS), and various focal epilepsy phenotypes [with hippocampal sclerosis (HS), lesions other than HS, lesionnegative]. The random-effects inverse-variance weighted (IVW) model was the primary method used, supported by heterogeneity and pleiotropy assessments. Multivariable Mendelian randomization analyses (MVMR) were used to identify micronutrients that are significantly causally associated with different epilepsy subtypes and to confirm the most potential causal risk factors for these subtypes. Results: Zinc conferred an increased risk of focal epilepsy with HS (OR = 1.01; p = 0.045). Carotene was similarly linked to higher risks of lesion-negative cases (OR = 1.129; p = 0.037). Conversely, vitamin B6 was associated with reduced risks of focal epilepsy with HS (OR = 0.949; p = 0.020), and vitamin D was linked to decreased risks of both CAE (OR = 0.976, 95% CI: 0.959-0.993, p = 0.006) and JAE (OR = 0.986, 95% CI: 0.973-0.999, p = 0.032). These associations were robust, showing minimal heterogeneity and no evidence of pleiotropy across various sensitivity analyses. After adjustment using MVMR, significant causal relationships between vitamin D and both CAE and JAE remained. Furthermore, the causal relationship between zinc and vitamin B6 on focal epilepsy with HS became non-significant, while carotene shifted from a risk factor to a protective factor for focal epilepsy lesion-negative after adjusting for vitamin D. Conclusion: MR estimates provide robust evidence for the causal effects of vitamin D on reducing the risk of CAE, and JAE, which might provide alternative treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Caregivers' knowledge and attitudes influence help-seeking behavior and treatment decisions of patients with epilepsy, which in turn significantly impacts epilepsy care. In Ethiopia, epilepsy is often misunderstood, associated with misconceptions and accompanied by persistent negative attitudes. The objective of this study is to assess the knowledge, attitude, and practice of caregivers of children with epilepsy. Methods: We conducted a hospital-based survey at the Yekatit 12 Hospital Pediatric Neurology Clinic, Addis Ababa, Ethiopia, between May and July 2022. We invited caregivers of children with epilepsy taking one or more daily anti-seizure medications to participate. Caregivers were invited to complete a structured questionnaire with guidance from a trained nurse to estimate knowledge and attitudes towards epilepsy and its treatment. Knowledge and attitudes were categorized as "good" and "favorable" (correct answers to ≥ 50% of questions) or "bad" and "unfavorable" (< 50% correct answers), respectively. Attitudes towards standard care versus non-standard (e.g., spiritual) care were also estimated. Results: A total of 120 caregivers completed the questionnaire. Many caregivers were familiar with the term 'epilepsy', with more than half (51.7%) having heard or read about it previously. The reported causes of epilepsy varied, with birth injury being the most common cause (44 out of 120 caregivers). Notably, there was association between the caregiver's gender and their knowledge score, with a p-value = 0.05. Caregivers exposed to information about epilepsy through hearing or reading demonstrated significantly higher levels of knowledge, with a p-value < 0.001. Additionally, knowing someone with epilepsy other than the index child was significantly associated with higher knowledge scores (p-value < 0.001). The study also revealed negative attitudes toward epilepsy: for example, 56.7% of surveyed caregivers believed it is unlikely that a child with epilepsy has normal cognitive abilities and 39.1% believed they should never be allowed to attend regular school. Additionally, a high proportion of caregivers (70%) sought alternative treatments (e.g., spiritual help) alongside standard medical care. Conclusions: A significant knowledge gap was identified among caregivers, revealing prevalent misconceptions and negative attitudes. Improving epilepsy awareness, attitudes, and practices among caregivers will potentially contribute to overall improved quality of life for children with epilepsy. [ABSTRACT FROM AUTHOR]

Functional changes in the pediatric brain following neural injuries attest to remarkable feats of plasticity. Investigations of the neurobiological mechanisms that underlie this plasticity have largely focused on activation in the penumbra of the lesion or in contralesional, homotopic regions. Here, we adopt a whole-brain approach to evaluate the plasticity of the cortex in patients with large unilateral cortical resections due to drug-resistant childhood epilepsy. We compared the functional connectivity (FC) in patients' preserved hemisphere with the corresponding hemisphere of matched controls as they viewed and listened to a movie excerpt in a functional magnetic resonance imaging (fMRI) scanner. The preserved hemisphere was segmented into 180 and 200 parcels using two different anatomical atlases. We calculated all pairwise multivariate statistical dependencies between parcels, or parcel edges, and between 22 and 7 larger-scale functional networks, or network edges, aggregated from the smaller parcel edges. Both the left and right hemisphere-preserved patient groups had widespread reductions in FC relative to matched controls, particularly for within-network edges. A case series analysis further uncovered subclusters of patients with distinctive edgewise changes relative to controls, illustrating individual postoperative connectivity profiles. The large-scale differences in networks of the preserved hemisphere potentially reflect plasticity in the service of maintained and/or retained cognitive function. [ABSTRACT FROM AUTHOR]

Background: The primary aims of our cross-sectional observational study were: (i) to determine the prevalence of depressive symptoms in children and adolescents with epilepsy compared to controls and (ii) to explore the difference in depressive symptoms in patients with epilepsy only and those with epilepsy and primary headache as a comorbidity. The secondary objective was to explore parental stress levels. Methods: 68 pediatric patients aged 6-18 years (44 with epilepsy only and 24 with epilepsy and headache) and 50 controls were recruited. Depressive profile and parental stress were assessed using Children's Depression Inventory, Second Edition (CDI-2) and Parenting Stress Index-Short Form (PSI-SF). Results: The group with epilepsy showed significantly high depressive symptoms and parental stress compared to controls. The patients with headache in comorbidity experienced more depressive symptoms than those with epilepsy only. Conclusion: Depressive symptoms are more prevalent in patients who have comorbid epilepsy and primary headache; therefore, the neurological/psychological mechanisms underlying this condition should be further investigated. The simultaneous presence of epilepsy, headache and depressive symptoms impacts the quality of life of patients and their parents, increasing parental stress and family management. [ABSTRACT FROM AUTHOR]

Background: Epileptic children can pose an additional risk of poor bone health; this study aimed to evaluate the influence of anti-seizure medications (ASMs) on vitamin D level and sclerostin as a bone turnover biomarker in children with epilepsy. Subject and methods: This case–control comparative study was conducted on 180 children aged from 5–18 years diagnosed with epilepsy according to the definition of the International League Against Epilepsy on ASMs for more than 3 months and were classified into 90 epileptic children on ASM monotherapy and 90 epileptic children on ASM polytherapy, in addition to 90 healthy children age- and sex-matched who served as controls. After obtaining basic data, laboratory investigations were performed, including serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, vitamin D, and serum sclerostin. Results: When we compared epileptic patients to the control group, there was a statistically significant low level of vitamin D, calcium, and phosphorus and a high level of sclerostin among both epileptic groups with mono or polytherapy. Sclerostin has a statistically significant negative correlation with vitamin D, alkaline phosphatase and parathyroid hormone. Additionally, it has a negative correlation with serum phosphorus, but without a significant correlation. On the other hand, sclerostin has a statistically positive correlation with age and serum calcium, but without a significant correlation. Multiple linear regression analyses were conducted to predict the contributing factors of sclerostin. Only duration of treatment and BMI were significant predictors of high levels of sclerostin. In contrast, the other factors failed to show any significant contribution. Conclusion: The present study showed that ASMs modulate the serum levels of sclerostin and vitamin D hence, might be involved in their adverse effects on bone. [ABSTRACT FROM AUTHOR]

Dysautonomic disorders are an increasingly studied group of conditions, either as isolated diseases or associated with other neurological disorders. There is growing interest in understanding how dysautonomia affects people with epilepsy, who may report autonomic symptoms before, during and after seizures. Furthermore, autonomic abnormalities appear to play a role in sudden unexpected death in epilepsy, likely contributing to the increased mortality rate described in epilepsy. To better understand the association between epilepsy and dysautonomia, we explored electrochemical skin conductance in a group of 18 children and young adults with epilepsy compared to 15 age- and sex-matched healthy controls by the SudoscanTM test. We found a significant difference in terms of electrochemical skin conductance, suggesting that people with epilepsy suffer significantly reduced conductance in small nerve fibers. Within patients, values were significantly different according to the type of epilepsy and to neuroimaging results, with lower conductance values in epilepsies of unknown origin and in patients with morphological abnormalities of the brain. Using a non-invasive test, we identified altered conductance of small sympathetic nerve fibers in children and young adults with epilepsy, suggesting underlying dysautonomia. Further studies are needed to investigate this association and to clarify its neurobiological substrates. [ABSTRACT FROM AUTHOR]

• There is a strong and negative correlation between the fear experienced by parents about epilepsy during the COVID-19 period and the seizure self-efficacy of children with epilepsy. • As the fear experienced by parents about epilepsy during the COVID-19 period increased, the seizure self-efficacy of children with epilepsy decreased. • As the seizure self-efficacy of children with epilepsy decreased, the fear experienced by parents about epilepsy during the COVID-19 period increased. Seizure-related self-efficacy is the belief individuals have that they can perform the necessary actions to cope effectively with their seizures. Determining, developing, strengthening, and maintaining the perception of self-efficacy in children with epilepsy facilitates the child's disease management and their ability to cope with it. This study aimed to assess the impact of epilepsy-related parental fears during the COVID-19 period on the seizure self-efficacy of their children. A total of 321 children with epilepsy and their parents participated in this descriptive, correlational, and cross-sectional study. Data were collected through the Descriptive Information Form, the Seizure Self-Efficacy Scale for Children (SSES-C), and the Epilepsy-Related Fears in Parents Questionnaire (EFPQ). Descriptive statistics, including frequency, percentage, and mean scores, were used to analyze the characteristics of the children and their parents. The Shapiro–Wilk test was utilized to assess the normality of the scale data. Pearson correlation analysis examined the relationship between parents' epilepsy-related fears and their children's seizure self-efficacy, while multiple regression analysis determined the effect of parental fears on children's seizure self-efficacy. The mean age of children included in the study was 12.65±2.37 years. Analysis revealed a strong and significant negative correlation between parents' epilepsy-related fears during the COVID-19 period and the seizure self-efficacy of their children. In the model created with regression analysis, The mean scores of parents on the short-term fears of parents about epilepsy of the EFPQ explained 85 % of children's seizure self-efficacy. The mean scores of parents on the long-term fears of parents about epilepsy of the EFPQ explained 85 % of children's seizure self-efficacy. It was determined that all of these variables together explained 85 % of the seizure self-efficacy of children with epilepsy. The findings of the study underscore the importance of addressing parents' fears regarding epilepsy, emphasizing the need for healthcare professionals to be aware of and provide support for these concerns. Future studies should focus on interventions to enhance the seizure self-efficacy of children with epilepsy. [ABSTRACT FROM AUTHOR]

The decision to treat children with benign epilepsy with centrotemporal spikes (BECTS) using antiseizure medications (ASM) is controversial. Our goal is to compare the effect of ASM treatment on the alteration of electroencephalographic (EEG) functional connectivity and power across four frequency bands in children with BECTS. Children with BECTS with two-year follow-up were retrospectively divided into ASM versus non-ASM groups. The network properties of the EEGs as based on network-based statistic and graph theory were evaluated by the following indices: global efficiency, clustering coefficient, betweenness centrality, and nodal strength in four frequency bands (delta, theta, alpha, and beta). EEG power including absolute power (AP) and relative power (RP) was analyzed in four frequency bands. In children with BECTS with ASM treatment, there was no significant change in EEG connectivity across all bands before and after two years of ASM. In children with BECTS without ASM treatment, there was a significant increase of global efficiency, clustering coefficient, and nodal strength but not the betweenness centrality in the delta band after two years of follow-up. A decrease in AP in the delta and theta bands and a decrease in RP in the theta band were found in the ASM group after two years of treatment. Our results suggest that ASM may play a role in modulating the development of increasing overall brain connectivity and in downregulating overt synaptic activity, but not intrinsic focal connectivity, in the early years of BECTS. The changes in the EEG power indicate that ASM significantly normalized slow-wave band power. [ABSTRACT FROM AUTHOR]

• Early detection of the onset of childhood absence seizures is mandatory to deliver an external stimulation able to inhibit them. • An on-line process is developed to detect the onset of absence seizures from four scalp EEG electrodes. • The proposed unsupervised solution detects most seizure onsets within a very short delay of 200 or 500 ms. This study aims to detect the seizure onset, in childhood absence epilepsy, as early as possible. Indeed, interfering with absence seizures with sensory simulation has been shown to be possible on the condition that the stimulation occurs soon enough after the seizure onset. We present four variations (two supervised, two unsupervised) of an algorithm designed to detect the onset of absence seizures from 4 scalp electrodes, and compare their performance with that of a state-of-the-art algorithm. We exploit the characteristic shape of spike-wave discharges to detect the seizure onset. Their performance is assessed on clinical electroencephalograms from 63 patients with confirmed childhood absence epilepsy. The proposed approaches succeed in early detection of the seizure onset, contrary to the classical detection algorithm. Indeed, the results clearly show the superiority of the proposed methods for small delays of detection, under 750 ms from the onset. The performance of the proposed unsupervised methods is equivalent to that of the supervised ones. The use of only four electrodes makes the pipeline suitable to be embedded in a wearable device. The proposed pipelines perform early detection of absence seizures, which constitutes a prerequisite for a closed-loop system. [ABSTRACT FROM AUTHOR]

Inflammatory cytokines participate in the pathology of epilepsy and the development of drug resistance. In this study, we combined a cytokine array and enzyme-linked immunosorbent assay to identify new cytokines in the plasma from children on early stage of the onset of epilepsy (EOE) and children with drug-resistant epilepsy (DRE). Compared with healthy controls, a broad up-regulation of cytokines was observed in patients with EOE, and many of the cytokines were not previously reported. In patients with DRE, most of these up-regulated cytokines maintained at relatively low levels close to those in controls; only a few of them, including CCL5, Serpin E1, and IGFBP2, remained at high levels. The dramatic difference in cytokine profile could be a strong clue for the incidence of DRE, and DRE-associated cytokines appeared to have the potential to be new biomarkers for epilepsy prognosis and therapeutic targets. [ABSTRACT FROM AUTHOR]

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy, and their representatives to develop minimum sets of standardized outcomes and outcome measurement methods for clinical practice. Using modified Delphi consensus methods with consecutive rounds of online voting over 12 months, a core set of outcomes and corresponding measurement tool packages to capture the outcomes were identified for infants, children, and adolescents with epilepsy. Consensus methods identified 20 core outcomes. In addition to the outcomes identified for the ICHOM Epilepsy adult standard set, behavioral, motor, and cognitive/language development outcomes were voted as essential for all infants and children with epilepsy. The proposed set of outcomes and measurement methods will facilitate the implementation of the use of patient‐centered outcomes in daily practice. [ABSTRACT FROM AUTHOR]

Objectives Understanding the parenting practices of parents of children with epilepsy can be a practical guide for care and education planners to prevent mental disorders in these children. This study aimed to explain the parenting practices of parents of children with epilepsy in Shahrekord. Materials & Methods This study is a qualitative study with conventional content analysis. Participants in the study consisted of 20 mothers with epileptic children in Shahrekord, who were included in the study by purposive sampling method with maximum variance in terms of child age, number of family children, and child sex. The data collection method was a semi-structured interview using the interview guide. Data analysis was performed using a conventional content analysis at the same time as data collection. Interviews continued until data saturation was reached. Results The present study revealed five main themes in discipline methods, including over-support / over-protection, forcing to support, rejecting, parental conflict in discipline methods, and using harmful discipline methods. Conclusion In conclusion, the experiences of mothers in the present study show that using inappropriate discipline methods can have adverse effects on the mental-emotional and social health of the child in the future and raise the need to design educational interventions to empower parents of epileptic children in coping with parenting stress effectively. [ABSTRACT FROM AUTHOR]

Childhood absence epilepsy (CAE) has a typical electroencephalography (EEG) pattern of generalized 3 Hz spike and wave discharges (SWD). Focal interictal discharges were also documented in a small number of documents. The aim was to investigate the amplitudes of interictal 3 Hz SWD within the 1st second in drug-naïve CAE patients. In this way, areas with maximal electronegativity at the beginning of clinically generalized discharges will be documented. The EEG records of children with drug-naïve CAE were evaluated retrospectively by two child neurologists first for 3 Hz SWD. Then, a machine-learning model evaluated the amplitudes of 3 Hz in the 1st second of SWD. Maximum electronegativity areas were documented and classified as focal, bilateral, and generalized. One hundred and twelve 3 Hz SWD were evaluated in 11 patients. Among discharges within the 1st second, maximum electronegativity areas were documented as focal for 44 (39.2%), bilateral for 8 (7.1%), generalized for 60 (53.5%). Among focal electronegativity areas, mostly right central, left occipital and midline parietal areas were documented in 12 (10.7%), 7 (6.2%), and 6 (5.3%), respectively. Eight (7.1%) of the maximum electronegativity areas were detected bilaterally, of which 7 (6.2%) originated from the frontopolar areas. Focal maximal electronegativity areas were frequently observed in drug-naïve CAE patients, comprising approximately half of non-generalized discharges. Focal discharges might be misleading in diagnosis. Focal areas within the brain may be responsible for and contribute to absence seizures that appear bilaterally symmetrical and generalized clinically. Although its clinical implication is unknown, this warrants further study. [ABSTRACT FROM AUTHOR]

L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare disorder. The patients have psychomotor retardation, ataxia, macrocephaly, and epilepsy usually in childhood. We present a case of L-2-HGA who developed dystonia in the third decade of life. The family reported symptoms of progressive psychomotor regression since childhood. On assessment, the patient had mild impairment of higher mental functions, mild exotropia, and right-hand dystonia. Brain MRI revealed diffuse bilateral symmetrical subcortical white matter hyperintense signals. 2-Hydroxyglutaric acid in urine was elevated and the whole genome sequencing revealed a homogeneous pathogenic variant of the L-2-hydroxyglutarate dehydrogenase (L2HGDH) gene. The prognosis was explained to the caregivers. Patients with mild phenotype L-2-HGA can remain undiagnosed until adulthood. Cases of dystonia even without complaints of epilepsy should be investigated by MRI -brain, urine test and genetic testing to rule out L-2-HGA. [ABSTRACT FROM AUTHOR]

Objectives We aimed to assess the serum levels of caspase-3 as a marker of apoptosis and microtubule-associated protein 1A/1B-light chain 3 (MAP1-LC3) as an autophagy marker in epileptic children with various clinical and pharmacological types. Methods This case–control study was carried out on 90 participants (50 pediatric patients with epilepsy and 40 healthy matched children), the patients were categorized into three groups: Group (A): 25 pharmacosensitive epilepsy, Group (B): 25 pharmacoresistant epilepsy, and Group (C): 40 (age, sex, and body mass index) matched healthy children selected as controls. Serum caspase-3 and MAP1-LC3 were measured in all study groups, using commercially available ELISA kits. Results Serum caspase-3 was significantly higher among epileptic children, especially in the pharmacoresistant group, cases managed with multiple antiepileptic drugs, and cases with abnormal EEG findings. Conversely, circulating MAP1-LC3 levels showed a significant reduction in epilepsy cases, particularly in pharmacoresistant cases, in cases treated with multiple antiepileptic drugs, and in cases with abnormal EEG data. A significant negative correlation between serum caspase-3 and MAP1-LC3 was found among epileptic children (r = −0.369, p = 0.0083). Serum caspase-3 was a more valid biomarker in helping diagnose childhood epilepsy, while serum MAP1-LC3 was more valid in predicting pharmacoresistant type. Conclusion The study reveals that serum caspase-3 levels were significantly elevated, particularly in pharmacoresistant cases and those managed with multiple drugs. Conversely, MAP1-LC3 levels were significantly reduced in epilepsy cases, suggesting potential involvement of altered apoptosis and autophagy in childhood epilepsy. [ABSTRACT FROM AUTHOR]

Objectives The present study was designed to study the efficacy of sequential dietary therapy with a modified Atkins diet (mAD) followed by low glycemic index treatment (LGIT) in treating drug-resistant epilepsy in children. Methods This interventional study was conducted from February 2021 to February 2022 among children aged 6 months to 5 years who had failed to respond to more than two conventional and correctly chosen antiseizure medications. The primary endpoint was the proportion of good responders, that is, children with more than 50% seizure reduction. Secondary outcome measures were the proportion of children with seizure freedom, > 90% seizure reduction, and the nature of parent-reported adverse events. Results A total of 45 children were recruited for the study, with 6 children being lost to follow-up at 12 weeks. At 12 weeks, 30 of 39 (76.9%) children were good responders with more than 50% seizure reduction. Of these 30 children, 11 (24.4%) had more than 90% seizure reduction, with 9 (20%) achieving complete spasm freedom. Constipation was the most common side effect of the diet among the enrolled subjects. Conclusion Clinicians can consider sequential dietary therapy with a mAD in the first month followed by LGIT in the next 2 months for treating children who could not tolerate mAD beyond 1 month. [ABSTRACT FROM AUTHOR]

Significant pharmacokinetic (PK) differences exist between different forms of valproic acid (VPA), such as syrup and sustained‐release (SR) tablets. This study aimed to develop a population pharmacokinetic (PopPK) model for VPA in children with epilepsy and offer dose adjustment recommendation for switching dosage forms as needed. The study collected 1411 VPA steady‐state trough concentrations (Ctrough) from 617 children with epilepsy. Using NONMEM software, a PopPK model was developed, employing a stepwise approach to identify possible variables such as demographic information and concomitant medications. The final model underwent internal and external evaluation via graphical and statistical methods. Moreover, Monte Carlo simulations were used to generate a dose tailoring strategy for typical patients weighting 20–50 kg. As a result, the PK characteristics of VPA were described using a one‐compartment model with first‐order absorption. The absorption rate constant (ka) was set at 2.64 and 0.46 h−1 for syrup and SR tablets. Body weight and sex were identified as significant factors affecting VPA's pharmacokinetics. The final PopPK model demonstrated acceptable prediction performance and stability during internal and external evaluation. For children taking syrup, a daily dose of 25 mg/kg resulted in the highest probability of achieving the desired target Ctrough, while a dose of 20 mg/kg/day was appropriate for those taking SR tablets. In conclusion, we established a PopPK model for VPA in children with epilepsy to tailor VPA dosage when switching between syrup and SR tablets, aiming to improve plasma VPA concentrations fluctuations. [ABSTRACT FROM AUTHOR]

Epilepsy is a disorder characterized by abnormal brain neuron activity, predisposing individuals to seizures. The International League Against Epilepsy (ILAE) categorizes epilepsy into the following groups: focal, generalized, generalized and focal, and unknown. Infants are the most vulnerable pediatric group to the condition, with the cause of epilepsy development being attributed to congenital brain developmental defects, white matter damage, intraventricular hemorrhage, perinatal hypoxic-ischemic injury, perinatal stroke, or genetic factors such as mutations in the Sodium Channel Protein Type 1 Subunit Alpha (SCN1A) gene. Due to the risks associated with this condition, we have investigated how the latest pharmacological treatments for epilepsy in children impact the reduction or complete elimination of seizures. We reviewed literature from 2018 to 2024, focusing on the age group from 1 month to 18 years old, with some studies including this age group as well as older individuals. The significance of this review is to present and compile research findings on the latest antiseizure drugs (ASDs), their effectiveness, dosing, and adverse effects in the pediatric population, which can contribute to selecting the best drug for a particular patient. The medications described in this review have shown significant efficacy and safety in the studied patient group, outweighing the observed adverse effects. The main aim of this review is to provide a comprehensive summary of the current state of knowledge regarding the newest pharmacotherapy for childhood epilepsy. [ABSTRACT FROM AUTHOR]

Objective: Epilepsy patients exhibit considerable differences in their response to sodium valproate (VPA) therapy, a phenomenon that might be attributed to individual genetic variances. The role of genetic variations, specifically in sodium channels encoded by SCN1A and SCN2A genes, in influencing the effectiveness of VPA in treating epilepsy is still debated. This research focuses on examining the impact of these genetic polymorphisms on the efficacy of VPA therapy among pediatric epilepsy patients in China. Methods: Five single nucleotide polymorphisms (SNPs), including SCN1A (rs10188577, rs2298771, rs3812718) and SCN2A (rs2304016, rs17183814), were genotyped in 233 epilepsy patients undergoing VPA therapy. The associations between genotypes and the antiepileptic effects of VPA were assessed, with 128 patients categorized as VPA responders and 105 as VPA non-responders. Results: In the context of VPA monotherapy, SCN1A rs2298771 and SCN2A rs17183814 were found to be significantly associated with VPA response (P< 0.05). Conclusion: Our study suggests the findings of this investigation indicate that the polymorphisms SCN1A rs2298771 and SCN2A rs17183814 could potentially act as predictive biomarkers for the responsiveness to VPA among Chinese epilepsy patients. [ABSTRACT FROM AUTHOR]