Epilepsy Group Research Articles

Beyond Seizures: Psychiatric comorbidities in children with epilepsy.

Children with epilepsy are at an increased risk of developing psychiatric comorbidities, which exacerbate the overall disease burden. However, these disorders are often underreported in developing countries. This study, conducted in a developing country, aims to evaluate the frequency of psychiatric disorders and associated factors in a large cohort of children with epilepsy. This study is part of a large, ongoing prospective study on a cohort of children with epilepsy in Lebanon. Children were recruited at the onset of their seizures between March 2010 and May 2016 and were followed for periods ranging from 2 to 12years. The medical records of 598 children with new-onset seizures were analyzed throughout their follow-up period to identify the presence of any psychiatric disorders. Psychiatric disorders were classified as internalizing or externalizing disorders based on DSM-5 criteria and were considered present if the child had been referred and diagnosed by a pediatric psychiatrist, therapist, or neurologist, or if the medical record provided clear evidence of the child taking medication for a psychiatric disorder. Multivariable logistic regression was used to identify factors associated with psychiatric disorders. Of the 598 children with new onset seizures, 75 (12.5%) were diagnosed with a psychiatric disorder, with 30 (5.0%) having an internalizing disorder and 47 (7.9%) having an externalizing disorder. Externalizing psychiatric disorders were most commonly reported children with developmental epileptic encephalopathies (18.2%) compared to other epilepsy groups. Intellectual and developmental delay was the most important factor associated with externalizing disorders (OR 3.36, 95%CI 1.48-7.62, p=0.004). In contrast, the frequency of internalizing disorders didn't differ across epilepsy groups. The most significant factors associated with the occurrence of internalizing psychiatric comorbidity were the failure of at least two antiseizure medications (OR 3.25, 95% CI 1.37-7.71, p=0.007) and an older age at seizure onset (> 10years vs.<2 years, OR 6.86, 95% CI 1.49-31.57, p=0.013). The prevalence of diagnosed psychiatric comorbidities in children with epilepsy in this study was lower than previously reported in developed countries. This may indicate potential underreporting of psychiatric disorders in Lebanon, where local practices may prioritize epilepsy management over mental health. This study highlights the need for systematic psychiatric screening during routine clinic visits, particularly for children with intellectual or developmental delays and those with poor seizure control.

Identification and verification of autophagy-related gene signatures and their association with immune infiltration and drug responsiveness in epilepsy

BackgroundEpilepsy, a common neurological disorder, is characterized by susceptibility to recurrent seizures. Increasing evidence suggests that autophagy plays a crucial role in the initiation and progression of epilepsy. However, the precise mechanisms by which autophagy deficiencies involved in epileptogenesis are still not fully understood.MethodsTwo datasets of epilepsy (GSE143272 and GSE256068) were downloaded from the Gene Expression Omnibus (GEO) database. Differential expression genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA) were employed to screen for autophagy related differential expression genes (ARDEGs) in GSE143272 database. Subsequently, protein–protein interaction, transcription factors and miRNAs networks were constructed. Additionally, the functional enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied. The hub ARDEGs were identified through CytoHubba, followed by the LASSO analysis. The Immune Cell Abundance Identifier (ImmuCellAI) was used to estimate peripheral immune cells abundance of epilepsy. Furthermore, the expression level of hub ARDEGs were detected in patients treated with different epilepsy monotherapies to explore the role of autophagy in the responsiveness of antiepileptic drug therapy. Finally, the expression level of hub ARDEGs were further validated in hippocampus of GSE256068 to enhance the reliability of the results.ResultsTwenty ARDEGs in epilepsy were screened out by integrating DEGs and WGCNA analysis. KEGG enrichment analysis showed that the ARDEGs in epilepsy were not only involved in the autophagy, but also apoptosis, the NOD-like receptor signaling pathway, the neurotrophin signaling pathway, etc. Four hub ARDEGs (PIK3R1, TRIM21, TRIM22, and ITPR3) were screened through integrating CytoHubba plug and LASSO analysis. The immune infiltration analysis showed that there was a significantly increased abundance of macrophages and a decreased abundance of CD4 and CD8 T cells, including Tr1, nTreg, Tfh, CD8 naïve, cytotoxic T cells and effector memory T cells in the epilepsy group. Furthermore, the hub ARDEGs were significantly correlated with the abundance of differential immune cells. In expression level validation and anti-epileptic drug responsiveness analysis, PIK3R1 and ITPR3 had significant differences in the hippocampus of patients with epilepsy. PIK3R1 expression level was found to be related with carbamazepine resistance.ConclusionThis study elucidated the autophagy-related gene signatures in epilepsy and clarified their association with immune infiltration and anti-epileptic drug responsiveness, providing a novel target for future therapeutic interventions and disease markers in epilepsy.

Phagocytic Function Analyses of GABBR-Related Microglia in Immature Developing Epileptic Brain Based on 10× Single-Nucleus RNA Sequencing Technology

Background: Epilepsy is a neurological disorder defined by the occurrence of epileptic seizures, which can significantly affect children, often leading to learning and cognitive impairments. Microglia, the resident immune cells of the central nervous system, are essential in clearing damaged neurons through phagocytosis. Notably, GABBR-associated microglia have been implicated in regulating phagocytic activity. Since the phagocytic function of microglia is critical in the pathogenesis of epilepsy, this study aims to investigate the role of GABBR-associated microglia in the development of the immature brain following epileptic seizures. Methods: Epilepsy was induced in a mouse model by the intraperitoneal injection of KA. Changes in the expression of the GABBR-related gene, GABBR2, in hippocampal microglia were analyzed using single-nucleus RNA sequencing (snRNA-seq). Cognitive and emotional changes in the mice were assessed through behavioral analyses. The expression of GABBR2 was semi-quantitatively measured using Western blotting, quantitative reverse transcription PCR, and immunofluorescence. Additionally, the spatial relationship between GABBR2 and hippocampal neurons was evaluated using Imaris software. Results: The snRNA-seq analysis revealed that GABBR2 expression was elevated in activated microglia in the hippocampus during chronic epilepsy compared to the early phase of seizures. Behavioral assessments demonstrated heightened anxiety levels and learning and memory impairments in the chronic epilepsy group compared to the control group. GABBR2 expression was upregulated in chronic epilepsy. Three-dimensional reconstruction analyses revealed a significantly increased contact volume between GABBR-associated microglia and neurons in the chronic epilepsy group compared to the control group. Conclusions: GABBR-associated microglia significantly contribute to the progression of immature brain diseases by promoting neuronal phagocytic activity.

Knowledge, attitude and perception of epilepsy patients toward epilepsy surgery at Jordan University hospital.

Epilepsy is a condition associated with stigma and considerable morbidity, placing a significant burden on patients and their families. It is fundamental to be mindful of the fact that a substantial number of patients remain unaware of the effective surgical procedures that have shown great success in many cases, drawing upon the global underutilization of epilepsy surgery (ES). In this study, we explore the knowledge and attitudes of epilepsy patients towards ES at Jordan University Hospital (JUH). This study aims to evaluate epilepsy patients' attitudes and knowledge regarding ES at JUH, identify the variables affecting their attitudes, and compare the results with other Middle Eastern and Western reports. In this cross-sectional study, conducted between the 1st of March and the 1st of September 2023, we gathered and analyzed data from epilepsy patients in the neurology clinic at JUH. A self-administered questionnaire was utilized, with questions emphasizing patients' demographics, disease status, and their knowledge and attitude toward ES. In order to determine the predictors of attitude, logistic regression was performed on the univariate analysis using the SPSS software. This study included 145 participants, most of them within the 17 and 29 age group, and a mean age at first seizure of 21.6years. Our sample included more generalized than focal epilepsy patients, with an additional 30% of patients being unaware of their specific seizure type. 46% of patients were on at least 2 antiepileptic drugs (AEDs), especially among the focal epilepsy group and 61% were non-adherent to their medications. Eighty-two participants (57%) were aware of ES, yet only twenty-five have shown a high level of understanding. The majority of patients (77%) have expressed a positive attitude towards ES. Although patients' attitude was significantly associated with their first impression towards ES, age, age at first seizure and not possessing a driving license, the regression model did not reveal significant predictors. Despite the perception of 94% of the patients that ES has a moderate to high risk, this did not have any significant influence on their final attitude. Furthermore, our results concluded that income, insurance type, educational level, frequency of seizures, and poor academic outcome played no significant role in patients' final attitude towards ES. ES is no longer considered an "experimental" or "last resort" treatment option. The results emphasize the importance of adapting educational interventions to improve knowledge and understanding of ES and implement measures to surgically pre-evaluate potential candidates. Further research should be done to overcome and address this gap in underutilization. In our study, we conclude that this gap is still present especially in people who are in need and may potentially be candidates for ES, but with the displayed positive attitude in the majority of our patients we are optimistic that the remaining barriers can be overcome, and that the results obtained from our study will be helpful for positive advancements in patients' quality of life.

Evaluation of risk factors for metabolic syndrome in epileptic patients in Palembang, Indonesia: a hospital-based and case-control study

&amp;lt;p style=&amp;quot;font-size: 11pt; color: #000000; font-weight: 400;&amp;quot;&amp;gt;&amp;lt;strong&amp;gt;Aim&amp;lt;/strong&amp;gt; To examine the association between metabolic syndrome and risk factors in epileptic patients at Dr. Mohammad Hoesin General Hospital in Palembang, Indonesia.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Methods&amp;lt;/strong&amp;gt; A hospital-based comparative case control research was conducted from July to September 2023. A total of 102 patients in the epilepsy group and 102 in the control group participated in this study. We conducted the data collection approach in three stages: a questionnaire, anthropometric measures and biochemical analysis.&amp;amp;nbsp;&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Results&amp;lt;/strong&amp;gt; Epilepsy patients were more likely to develop metabolic syndrome than the controls. The epilepsy group exhibited higher triglycerides, fasting blood sugar, and lower high density lipoprotein (HDL) values than the control group. The epilepsy group exhibited sedentary behaviour, while the control group had moderate to intense physical activity (p&amp;amp;lt;0.05). Epilepsy patients who take polytherapy, or several antiepileptic drugs, were 8.43 times more likely to develop metabolic syndrome (OR=8.43; 95%CI=1.45-32.12). Epilepsy patients with body mass index (BMI) &amp;amp;gt;25 had 1.57 times the risk of metabolic syndrome (OR=1.57; 95%CI=1.16-2.34). Epilepsy patients with total cholesterol levels &amp;amp;gt;200 mg/dL have a 5.81-fold higher risk of metabolic syndrome (OR=5.81; 95%CI=1.23-23.32).&amp;amp;nbsp;&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Conclusion&amp;lt;/strong&amp;gt; Our study found that more than a quarter of epilepsy patients have metabolic syndrome. The main risk factors for metabolic syndrome in epilepsy patients were a sedentary lifestyle, several antiepileptic medications, overweight, and increased total cholesterol levels.&amp;lt;/p&amp;gt;

Circulating microRNAs as Biomarkers of Various Forms of Epilepsy.

Background: Epilepsy is a group of disorders characterized by a cluster of clinical and EEG signs leading to the formation of abnormal synchronous excitation of neurons in the brain. It is one of the most common neurological disorders worldwide; and is characterized by aberrant expression patterns; both at the level of matrix transcripts and at the level of regulatory RNA sequences. Aberrant expression of a number of microRNAs can mark a particular epileptic syndrome; which will improve the quality of differential diagnosis. Materials and Methods: In this work; the expression profile of six microRNAs was analyzed: hsa-miR-106b-5p; hsa-miR-134-5p; hsa-miR-122-5p; hsa-miR-132-3p; hsa-miR-155-5p; and hsa-miR-206-5p in the blood plasma of patients suffering from temporal lobe epilepsy (n = 52) and juvenile myoclonic epilepsy (n = 42); n-amount of participants; in comparison with healthy volunteers. The expression analysis was carried out using RT-PCR. Mathematical processing of the data was carried out according to the Livak method. Results: A statistically significant change in the expression of hsa-miR-106b-5p; hsa-miR-134-5p; hsa-miR-122-5p; and hsa-miR-132-3p was found. An increase in the expression of hsa-miR-134-5p and hsa-miR-122-5p was registered in the group of patients with temporal lobe epilepsy compared to the control; as well as an increase in the expression of hsa-miR-132-3p and hsa-miR-106b-5p in the juvenile myoclonic epilepsy group compared to the control. hsa-miR-122-5p; 106b-5p; 132-3p are also able to discriminate groups with different syndromes. Additionally; a number of microRNAs are able to discriminate patients with drug-resistant and drug-sensitive forms of epilepsy from the control; as well as patients with hippocampal sclerosis and patients without hippocampal sclerosis from the control. Conclusion. Our data allow us to propose these microRNAs as plasma biomarkers of various epileptic syndromes.

Prevalence of and risk factors for sarcopenia in patients with epilepsy.

Epilepsy is a chronic neurological disorder with a burden of comorbidities. Knowledge regarding sarcopenia prevalence and associated risk factors in patients with epilepsy remains limited, which prompted us to conduct the present study. This cross-sectional study enrolled patients with epilepsy from our epilepsy clinic and controls from the staff at National Cheng Kung University Hospital, Tainan, Taiwan. Sarcopenia was defined using the criteria outlined by the 2019 Asian Working Group for Sarcopenia and the 2010 European Working Group on Sarcopenia in Older People. Muscle mass (skeletal muscle mass index) was measured through bioelectrical impedance, muscle strength was assessed using hand grip tests, and physical performance was evaluated using the 6-m walk test. Hormone (testosterone, growth hormone, and insulin-like growth factor-1) and vitamin D levels were measured. Descriptive statistics and logistic regression models were used to estimate the prevalence of sarcopenia and identify sarcopenia risk factors in patients with epilepsy. This study enrolled 300 adults (mean age: 42.9 ± 14.7 years; women: 53.7 %). The epilepsy and control groups comprised 200 and 100 participants, respectively. The overall prevalence of sarcopenia was 31.3 % and it was significantly higher (p = 0.004) in women (20.7 %) than in men (10.6 %). The prevalence was higher in the epilepsy group than in the control group (36.0 % vs. 22.0 %, p = 0.014). Logistic regression revealed female, age (≥ 65 year) and low body mass index (BMI) were influenced the risk of sarcopenia in all participants. Importantly, epilepsy is significantly associated sarcopenia. The BMI, protein level, calf circumference, and use of enzyme-inducing antiseizure medications (EIASM) influenced the risk of sarcopenia in the epilepsy group. The prevalence of sarcopenia is significantly higher in patients with epilepsy than in the control participants. Low BMI, protein level, calf circumference, and the use of EIASM may increase the risk of sarcopenia in this population. Our findings underscore the need for mitigating sarcopenia risk in patients with epilepsy.

Association between maternal usage of volatile organic compounds and West syndrome, the Japan Environment and Children’s study

Multiple etiologies of West syndrome have been reported; however, there are cases of unknown etiologies. Exposure to volatile organic compounds (VOCs) increases the risk of epilepsy; however, their effects on children remain unknown. This study aimed to investigate the association between maternal occupational usage of VOCs and West syndrome development in children. Using data from a cohort of 88,280 children, we extracted children born to mothers who had used VOCs during pregnancy. Based on an epilepsy diagnosis by the age of 2 years, the frequency of usage of VOCs was comparatively analyzed among the following groups: never diagnosed with epilepsy, West syndrome, and other epileptic syndromes. A total of 15, 154, and 88,111 children were categorized into the West syndrome, other epileptic syndrome, and never diagnosed with epilepsy groups, respectively. The odds ratio (OR) for West syndrome development increased with the frequency of permanent marker usage (one to three times a month: OR = 2.58, 95% confidence interval [CI] 0.75–8.90; one or more times a week: OR = 4.34, 95% CI 1.23–15.26). These results suggested an association between maternal occupational frequent usage of permanent marker and West syndrome development in children.

Increased Expression of MST1 in Patients With Epilepsy and in a Rat Model of Epilepsy.

Mammalian sterile20-like kinase 1 (MST1), a serine/threonine kinase frequently expressed, has emerged as pivotal modulator of multiple physiological and pathological conditions such as cellular growth, programmed cell death, oxidative stress, neurodegeneration, inflammation, and synaptic plasticity in the central nervous system. Various neurological diseases are associated with the activation of MST1. Epilepsy is a severe neurological disorder characterized by abrupt abnormal electrical activity in the brain and recurring spontaneous seizures. The most common pathological discoveries in patients and animal models with epilepsy are neuronal death, inflammation, neurodegeneration, neurogenesis, and axonal regrowth. The purpose of this study was to assess the levels of MST1 in serum and cerebrospinal fluid (CSF) specimens obtained from individuals diagnosed with epilepsy. In addition, it aimed to explore the expression pattern of MST1 in brain tissues of epileptic rats. We used enzyme-linked immunosorbent assay to measure the levels of CSF and serum MST1 in 10 epilepsy patients and 9 control patients. After creation of epilepsy models with healthy male Sprague-Dawley rats using lithium and pilocarpine, the expression of MST1 in the temporal cortex and hippocampus was evaluated at different time points (6h, 24h, 3days, 7days, 14days, and 30days after seizures) using immunofluorescence, immunohistochemistry, and Western blotting. In patients with epilepsy, the levels of CSF-MST1 were elevated (593.90±16.28 vs. 560.40±19.42pg/mL, p<0.05) compared to the control group. Accordingly, the serum-MST1 levels were 583.40±19.70pg/mL in the epilepsy group and 555.70±20.14pg/mL in the control group, demonstrating a statistically significant distinction (p<0.05). Levels of MST1 in CSF and serum could be of diagnostic help. Neuronal apoptosis in temporal cortex and hippocampus of epileptic rats was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. MST1 was expressed in the neuronal membrane and cytoplasm of the temporal cortex and hippocampus. The expression of MST1 increased after seizures, showing a relatively high level within 30days and reaching its highest point on the seventh day after status epilepticus. The findings of this study indicate that the increased expression of MST1 protein in patients with epilepsy and epileptic rats might play a role in the development of epilepsy.

Comparison of time perception in individuals between focal and generalized epilepsy.

Numerous cognitive impairments have been documented in patients with epilepsy, particularly in relation to memory and executive functions. However, research on time perception is relatively limited and primarily focuses on temporal lobe epilepsy. The current study seeks to compare time perception performance between patients with focal epilepsy and those with generalized epilepsy. A total of fifty-one individuals diagnosed with focal epilepsy and fifty-one individuals diagnosed with generalized epilepsy, which were monitored at the Epilepsy and Sleep Center, participated in this study. Initially, participants were asked to complete the Patient Health Questionnaire-9 (PHQ-9). Following this, they underwent computer-based assessments of time perception, which included the Time Estimation Test (TIET) and the Time Interval Production Test (TIPT). The intervals assessed were 4, 7, 32, and 58s. The mean age of the sample was 32.65years (±1.28). The sample consisted of 36 male and 66 female participants. The mean number of years of education was 12.3years, while the mean age at disease onset was 18.7years, and the mean duration of the disease was 13.8years. The TIPT ratio was significantly lower in the focal epilepsy group, with recorded values of 4s (Z = -2.540; p=0.011) and 7s (Z = -2.274; p=0.023). No significant differences were observed in other parameters of time perception. Research has demonstrated notable differences in time perception between individuals diagnosed with focal epilepsy and those with generalized epilepsy. The results suggest that time perception is more profoundly affected in patients with focal epilepsy in comparison to their counterparts with generalized epilepsy. Further comprehensive studies are necessary to explore the neural mechanisms that contribute to this disparity.

Mechanistic insights into Quetiapine's Protective effects on cognitive function and synaptic plasticity in epileptic rats.

The study aimed to examine the effects of Quetiapine, an atypical antipsychotic medication with purported neuroprotective qualities, on cognitive function and synaptic plasticity in epileptic rats. This investigation also sought to elucidate the mechanisms by which quetiapine influences the activity of the cyclic adenylate response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway and metallomatrix proteinase-9 (MMP9) expression in the context of epilepsy. The epileptic model was induced in rats through the administration of pilocarpine, with normal rats serving as the control group. Within the epilepsy group, two subgroups were established: one receiving normal saline and the other receiving quetiapine. Behavioral assays were utilized to assess learning, memory, and spatial exploration abilities. Furthermore, Western blot analysis, immunohistochemistry (IHC), and immunofluorescence (IF) staining were employed to evaluate the activity of the CREB/BDNF pathway, expression of MMP9 protein, and levels of synaptic plasticity-related proteins. Our study revealed that Quetiapine administration led to a notable enhancement in learning and memory in epileptic rats, as indicated by heightened drinking durations and visitation rates in behavioral assessments. Furthermore, Quetiapine upregulated the expression of pro-BDNF, m-BDNF, p-CREB, and CREB within the hippocampus, along with elevating mRNA levels of BDNF and CREB. Additionally, Quetiapine suppressed MMP-9 expression and promoted synaptic plasticity by augmenting SYN and PSD-95 expression levels in the hippocampus. Therefore, Quetiapine improved cognitive functions such as learning, memory, and spatial exploration in epileptic rats. Moreover, Quetiapine activated the CREB/BDNF signaling pathway, suppressed MMP-9 expression, and promoted synaptic plasticity.

One-year follow-up of neurobehavioral therapy in functional seizures or epilepsy with traumatic brain injury: A nonrandomized controlled trial.

Patients with traumatic brain injury (TBI) often present with seizures (functional and/or epileptic), but treatments for patients with TBI and seizures are limited. We examined treatment phase and 1-year post-enrollment outcomes following neurobehavioral therapy (NBT) for patients with TBI + functional seizures (FS) and TBI + epilepsy. In this multicenter, prospective, three-group, nonrandomized, controlled trial, with 1-year post-enrollment follow-up, three cohorts of adults were recruited: TBI + video-electroencephalography (EEG)-confirmed FS (n = 89), TBI + EEG-confirmed epilepsy (n = 29), and chart/history-confirmed TBI without seizures (n = 75). Exclusion criteria were recent psychotic or self-injurious behavior, current suicidal ideation, pending litigation or long-term disability, active substance use disorder, and inability to participate in study procedures. TBI + FS and TBI + epilepsy groups completed NBT for seizures, an evidence-based, 12-session, multimodal psychotherapy, whereas TBI without seizures participants received standard medical care. The primary outcome was change in seizure frequency; secondary outcomes were changes in mental health, TBI-related symptoms, disability, and quality of life. Reductions in average monthly seizures occurred during treatment in TBI + FS participants (p = .002) and were significant from baseline (mean = 16.75; 95% confidence interval [CI] = 11.44-24.53) to 12 months post-enrollment (mean = 7.28, 95% CI = 4.37-12.13, p = .002, d = .38). Monthly seizures decreased during treatment in TBI + epilepsy participants (p = .002); reductions were not statistically significant from baseline (mean = 2.38, 95% CI = 1.12-5.04) to 12-month postenrollment (mean = .98, 95% CI = .40-2.42, p = .07, d = .22). Regarding treatment-phase changes in secondary outcome measures, TBI + FS participants improved significantly on 10 of 19 variables (52.6%), TBI + epilepsy participants improved on five of 19 (26.3%), and TBI-onlycomparisons improved on only one of 19 (5.3%). NBT benefited patients with TBI + FS and TBI + epilepsy. Improvements were demonstrated at 1 year post-enrollment in those with TBI + FS. NBT may be a clinically useful treatment for patients with seizures.

Comparison of Premature Ejaculation in Men with Focal Epilepsy and Generalized Tonic-Clonic Epilepsy

Abstract Introduction premature ejaculation (PE) is one of the most common sexual disorders in men. Objectives Considering the importance of sexual health in men, especially patients with epilepsy, this study was conducted with the aim of comparing premature ejaculation in men with focal epilepsy and generalized tonic-clonic seizure (GTCS). Methods In this cross-sectional and observational study, patients with epilepsy were included in the study. The examined patients were examined by psychiatrists and neurologists, and sampling was done according to the entry and exit criteria. The total sample size was 200 people, including 100 patients with focal epilepsy and 100 patients with GTCS. The tools used included demographic profile form, Men Sexual Health Questionnaire (MSHQ), Sexual Quality of Life-Men (SQOL-M), and Premature Ejaculation Diagnostic Tool (PEDT). The study was conducted to include patients referred to specialized clinics and hospitals and who had the necessary conditions to participate in the study. Considering that all the patients were male, the questioning was done by a male researcher. Then, the extracted data were entered into SPSS statistical software. Results Result showed, the M(SD) age of the patients in the focal epilepsy group was equal to 30.18(3.85). M(SD) score of MSHQ tool was equal to 51.81 (11.98), SQOL-M tool was equal to 34.75 (9.36) and PEDT tool was equal to 8.63 (4.79). In this study, although the M(SD) of the PE score in the focal epilepsy group was reported to be 9.17 (4.49) higher than that of the GTCS group with a rate of 8.09 (5.04), but this difference was not significant. also, the findings showed that there was a significant relationship between the status of the PEDT score, the status of the SQOL-M score, and the MSH score (p &lt; 0.05). MSHQ score and SQOL-M score were reported to be lower in patients with PE disorder. Conclusion According to the findings, the prevalence of sexual disorders including PE in both groups of patients with epilepsy is significant. For this reason, it is necessary to carry out pharmacological and non-pharmacological interventions to reduce the rate of PE in these patients.

The asymptomatic bacteriuria in the patients with epilepsy: A cross-sectional study

BackgroundEpilepsy is a chronic neurological disorder characterized by repetitive unprovoked seizures. While certain anti-seizure medications have been linked to urinary tract infections, limited information exists on the occurrence and risk factors of asymptomatic bacteriuria (ASB) in individuals with epilepsy. This study aims to investigate the prevalence and factors associated with ASB in patients with epilepsy. MethodA cross-sectional study was conducted, enrolling patients with epilepsy and healthy adults as controls. All participants underwent urine analyses during follow-ups at an epilepsy special clinic. Data on epilepsy-related factors were thoroughly collected and analyzed. Descriptive statistics and a logistic regression model were employed to identify the prevalence and risk factors of ASB in patients with epilepsy. ResultsThe study encompassed 200 patients with epilepsy, compared to 100 healthy controls. The prevalence of ASB in the epilepsy group was significantly higher than in the healthy controls (34.0 % versus 16.2 %, p = 0.001). The logistic regression model identified factors statistically associated with ASB in epilepsy, including gender (female) (p < 0.001), proteinuria (p = 0.021), and the use of oxcarbazepine (p = 0.011). Interestingly, lamotrigine demonstrated a protective effect against ASB (p = 0.023), along with age (p = 0.015) in this study. Moreover, patients with and without ASB exhibited a similar rate of 12 months of seizure freedom. ConclusionThe prevalence of ASB is elevated in epilepsy, with identified risk factors including gender (female), proteinuria, and the use of the anti-seizure medication oxcarbazepine. Lamotrigine was found to be protective. These findings underscore the importance of clinician awareness, and careful monitoring of anti-seizure medication therapy.

Sleep Problems and Quality of Life in Children with Epilepsy Without Neurodevelopmental Disorders.

Background/Objectives: Sleep problems affect the quality of life (QoL) and treatment prognosis of children with epilepsy (CWE). We analyzed sleep problems and QoL in CWE but without neurodevelopmental disorders, which affect sleep and QoL. We also examined discrepancies between child self-reports and parent proxy reports in QoL assessments. Methods: Thirty-two CWE in grades 2-6 (aged 7-12 years) in regular classes who attended Osaka Metropolitan University Hospital and PL General Hospital between January 2022 and August 2023 were compared with 21 children who had attended the hospitals for acute non-neurological disorders and had recovered (control group). Children with neurodevelopmental disorders, those unable to answer questionnaires, and those taking sleeping pills were excluded. Children in both groups completed the Kinder Lebensqualität Fragebogen (KINDL-R); their parents completed the KINDL-R and Japanese Sleep Questionnaire for Elementary Schoolers (JSQ-ES). Results: There were no significant differences in mean (±SD) JSQ-ES total scores between the epilepsy and control groups (71.6 ± 21.4 vs. 63.2 ± 15.2, respectively; p = 0.16). In the epilepsy group, there were no significant differences in total or subscale KINDL-R scores between children with (JSQ-ES ≥ 80) and without (JSQ-ES < 80) sleep problems. Correlation coefficients between child self-reports and parent proxy reports for KINDL-R total scores were 0.171 (p = 0.348) and 0.656 (p = 0.001) for the epilepsy and control groups, respectively. There was a significant difference between the total scores of children's self-reports and parents' proxy reports in the control (p = 0.008) group, but not in the epilepsy group (p = 0.837). Conclusions: Sleep problems may not have significant impacts on the QoL of CWE without neurodevelopmental disorders. Parents of CWE do not always correctly assess their children's QoL, so it is important to ask both children and their parents to obtain a comprehensive picture of their QoL.

Visual acuity in the context of retinal neuroaxonal loss in people with epilepsy

Recent studies reported a significant retinal neuroaxonal loss in people with epilepsy (PWE). However, the impact of these structural alterations on visual function, i.e., visual acuity is yet unknown. In this prospective cohort study, 70 PWE and 76 healthy controls (HC), all aged 18-55 years, underwent an assessment of visual acuity with 100 % high contrast (HCVA) and 2.5 % low contrast (LCVA) Sloan letter charts. Thickness of the global peripapillary retinal nerve fiber layer (G-pRNFL) and volume of the ganglion cell inner plexiform layer (GCIP) were assessed with spectral-domain optical coherence tomography (OCT). For the statistical analyses, the epilepsy group was subdivided into PWE with sodium channel blocking (SCB)-drug intake (n = 52) and PWE without SCB-drug intake (n = 18), since an effect of SCB-drugs on visual perception has been reported previously. The overall PWE cohort presented significantly lower structural retinal measures, i.e., G-pRNFL thickness (97.57 ± 9.06 µm) and GCIP volume (1.99 ± 0.13 mm3) than HC (101.31 ± 8.28 µm, p = .01; 2.10 ± 0.15 mm3, p < .001). Subgroup analyses revealed that PWE who were treated with SCB-drugs had a significantly reduced G-pRNFL thickness (96.61 ± 9.70 µm, p = .01) and GCIP volume (1.98 ± 0.14mm3, p < .001) compared to HC, while PWE without SCB-drugs (100.36 ± 6.32 µm, 2.01 ± 0.13 mm3) did not differ from HC or PWE with SCB-drugs. In visual acuity tests (HCVA and LCVA), the overall PWE cohort (52.28 ± 8.56; 31.71 ± 8.49) scored significantly lower than HC (56.57 ± 4.74, p = .001; 35.13 ± 5.50, p = .04). In subgroup analyses only PWE with SCB-drugs presented significantly lower HCVA (51.25 ± 9.35, p = .003) and LCVA (30.04 ± 8.93, p = .03) scores compared to HC, while visual acuity scores did not differ between PWE without SCB-drugs (55.25 ± 4.75, 36.53 ± 4.50) and HC. PWE with SCB-drugs had significantly lower LCVA scores than PWE without SCB-drugs (p = .03). Importantly, no association was found between visual acuity scores and structural parameters, neither in the overall sample, nor in any of the subgroups. Retinal neuroaxonal loss in PWE was not associated with reduced visual acuity under high and low contrast. Instead, our findings reinforce SCB-drug intake as an important factor for reduced visual acuity under high and low contrast.

Trio-whole exome sequencing reveals the importance of de novo variants in children with intellectual disability and developmental delay

Understanding the genetic basis of developmental delay (DD) and intellectual disability (ID) remains a considerable clinical challenge. This study evaluated the clinical application of trio whole exome sequencing (WES) in children diagnosed with DD/ID. The study comprised 173 children with unexplained DD/ID. The participants underwent trio-WES and their demographic, clinical, and genetic characteristics were evaluated. Based on their clinical features, the participants were classified into two groups for further analysis: a syndromic DD/ID group and a non-syndromic DD/ID group. The genetic diagnostic yield of the 173 children diagnosed with DD/ID was 49.7% (86/173). This included 58 pathogenic or likely pathogenic single nucleotide variants (SNVs) in 41 genes identified across 54 individuals (31.2%) through trio-WES. Among these, 22 SNVs had not been previously reported. Additionally, 30 copy number variations (CNVs) were detected in 36 individuals (20.8%). The diagnostic yield in the syndromic DD/ID group was higher than that in the non-syndromic DD/ID group (57.8% vs. 47.2%, P < 0.001). Within the syndromic DD/ID subgroup, the diagnostic yield of the DD/ID with epilepsy subgroup (83.9%) was significantly higher than those of the other subgroups (P < 0.001). Based on the analysis of the individuals’ clinical phenotypes, the individuals with facial dysmorphism shown a higher diagnostic yield (68.2%, P < 0.001). The diagnostic yield of SNVs was higher in the individuals with DD/ID accompanied by epilepsy, whereas the diagnostic yield of CNVs was higher in the DD/ID without epilepsy group. Similarly, the diagnostic yield of de novo SNVs was higher in the DD/ID with epilepsy group, while the diagnostic yield of de novo CNVs was higher in the DD/ID without epilepsy group (all P < 0.001). Trio-WES is a crucial tool for the genetic diagnosis of DD/ID, demonstrating a diagnostic yield of up to 49.7%. De novo variants in autosomal dominant genes are significant contributors to DD/ID, particularly in non-consanguineous families.

Sleep-related epilepsies in the course of development in childhood

AbstractEpilepsy, as one of the most prevalent neurological diseases in childhood, has a strong reciprocal relationship with sleep. Sleep-associated epilepsy syndromes in childhood are mostly genetic and can be divided into (a) the group of self-limited focal epilepsies of childhood including self-limited epilepsy with autonomic seizures (SeLEAS) and self-limited epilepsy with centrotemporal spikes (SeLECTS) and (b) (non-self-limited) sleep-related hypermotor epilepsy (SHE). Sleep-accentuated (developmental and) epileptic encephalopathies (DEE/EE-SWAS, Landau–Kleffner syndrome [LKS]) are either genetic (possible transition from SeLEAS or SeLECTS) or structural, and they are characterized by continuous bilateral focal or generalized epileptic activity throughout the night with a clinical manifestation of stagnation or regression, in particular of cognition (verbal agnosia in LKS). Epilepsy syndromes with increased seizure frequency after sleep deprivation or with seizures in the transition to awakening include juvenile generalized epilepsy syndromes such as epilepsy with generalized tonic-clonic seizures alone (GTCA) or juvenile myoclonic epilepsy (JME), but also SeLECTS. Sleep is a very active process: Regeneration, reorganization, and consolidation of memory facilitate development and cognitive functioning. Epilepsy can alter sleep architecture and vice versa, which can appear as a vicious circle in epilepsies that are sleep related. Macrostructural elements of sleep such as sleep efficiency, sleep onset latency, wakefulness after sleep onset, REM and non-REM sleep fraction, as well as microstructural sleep elements such as slow-wave activity, slope of slow waves, cyclic alternating pattern (CAP), and physiological sleep figures, are important biomarkers with which to understand clinical symptoms such as cognitive stagnation and regression, to monitor treatment, but also to determine prognostic factors and will be an important tool for future studies.

Voltage-Gated Ion Channel Compensatory Effect in DEE: Implications for Future Therapies.

Developmental and Epileptic Encephalopathies (DEEs) represent a clinically and genetically heterogeneous group of rare and severe epilepsies. DEEs commonly begin early in infancy with frequent seizures of various types associated with intellectual disability and leading to a neurodevelopmental delay or regression. Disease-causing genomic variants have been identified in numerous genes and are implicated in over 100 types of DEEs. In this context, genes encoding voltage-gated ion channels (VGCs) play a significant role, and part of the large phenotypic variability observed in DEE patients carrying VGC mutations could be explained by the presence of genetic modifier alleles that can compensate for these mutations. This review will focus on the current knowledge of the compensatory effect of DEE-associated voltage-gated ion channels and their therapeutic implications in DEE. We will enter into detailed considerations regarding the sodium channels SCN1A, SCN2A, and SCN8A; the potassium channels KCNA1, KCNQ2, and KCNT1; and the calcium channels CACNA1A and CACNA1G.

Predictors of drug-resistant epilepsy in childhood epilepsy syndromes: A subgroup analysis from a prospective cohort study.

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.