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The aim of this study is to evaluate the utility of an artificial neural network (ANN) model in diagnosing idiopathic generalized epilepsy (IGE) and to compare the results of the diagnostic model constructed by combining the expression levels of miR‐146a, miR‐155, and miR‐132 genes using ANN, random forest (RF), and discriminant analysis (DA). qRT‐PCR is employed to determine the expression levels of the three miRNA genes. Forty‐six IGE patients and 51 healthy controls were included in the study. Three genetic biomarkers were employed to assess the discriminative power of the disease, and they were combined using ANN. Additionally, the performance of ANN was compared with RF and DA. Compared to healthy controls, the miR‐132 gene was significantly higher (p < 0.001) and the miR‐155 and miR‐146a genes were significantly lower in IGE patients (p < 0.001). The area under the curve (AUC) for predictions made by the ANN, RF, and DA were 0.96, 0.87, and 0.75, respectively, with accuracy rates of 0.96, 0.88, and 0.76, respectively. We demonstrate that ANN exhibits the highest accuracy, AUC, sensitivity, and specificity values among the three methods. The obtained results indicate that the combination of the three genes used as markers in IGE plays a significant role in the diagnosis of the disease. Instead of assessing biomarkers individually for the disease, combining them using machine learning methods leads to improved model performance. Additionally, not relying on a single genetic biomarker for the disease enables discrimination based on the collective impact of all biomarkers. [ABSTRACT FROM AUTHOR]

Objective: We evaluated huperzine A treatment in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) model of genetic generalized epilepsy (GGE) with absence seizures. Methods: Adult male GAERS (N = 15) were implanted with EEG recording electrodes 10 days before receiving study drug. Each animal received the following six treatments as a single, intraperitoneal dose, 7 days apart (in random order): huperzine A (0.3, 1.0, or 3.0 mg/kg), two periods of vehicle (0.9% NaCl), or ethosuximide (100 mg/kg) as a positive control. Electroencephalograms (EEGs) were acquired for 24 h before and after each treatment and analyzed for seizure activity during the 90‐min period immediately post‐treatment, including 30‐min intervals at 30, 60, and 90 min. Additional analyses evaluated seizure activity over the 24‐h post‐treatment period using 60‐min intervals at 6, 12, and 24 h. The cumulative 24‐h periods before and after each administered treatment were also compared. Results: Two‐way ANOVA showed a treatment difference [F(91,182) = 3.592, p < 0.0001] on the number of seizures over the first 90‐min post‐treatment (primary outcome); Tukey's post hoc analyses showed that, compared to vehicle, huperzine A (3.0 mg/kg) significantly reduced seizures in the 30‐min (p = 0.02) and 60‐min (p = 0.001) intervals, and ethosuximide significantly reduced seizures at all measured time intervals except the 1‐h blocks at 12 and 24 h. Huperzine A 3.0 mg/kg and ethosuximide significantly reduced seizures during the cumulative 24‐h post‐treatment period relative to pretreatment baseline. While huperzine A 3.0 mg/kg did not differ significantly from ethosuximide at any time point, the study was not designed to evaluate non‐inferiority. The only adverse event after huperzine A or ethosuximide was mild, dose‐dependent sedation. Significance: Huperzine A potently suppressed absence‐like seizures in GAERS, albeit with a shorter duration of action relative to ethosuximide, showing promise for clinical efficacy in GGE. Plain Language Summary: This study looked at how huperzine A affects seizures in rats with similar abnormal brain activity as seen in humans with absence epilepsy. Rats received different treatments, placebo (i.e., saline solution), huperzine A, and ethosuximide. Ethosuximide is considered a gold standard treatment for absence epilepsy. We recorded brain activity to measure seizures before and after each treatment. We found that huperzine A (3.0 mg/kg) reduced seizures soon after treatment, like ethosuximide. Both treatments appeared safe, causing only mild sleepiness. The study shows that huperzine A could be a good new treatment for a type of absence epilepsy. [ABSTRACT FROM AUTHOR]

Objective: This prospective study aimed to delineate the demographics, natural progression, and treatment response of patients newly diagnosed with epilepsy with generalized tonic–clonic seizures alone (EGTCA). Furthermore, our objective includes assessing the seizure recurrence rate post antiseizure medication (ASM) discontinuation within this cohort, alongside exploring predictive factors for seizure relapse. Methods: The study cohort, derived from an ongoing, prospective, multicenter investigation on children and adults with new‐onset unprovoked seizures, included consecutive patients enrolled between March 2010 and March 2020, and meeting mandatory ILAE criteria for EGTCA diagnosis. Participants underwent a 3‐h sleep‐deprived video‐EEG recording along with an epilepsy protocol brain magnetic resonance imaging (MRI) with repeat EEG at each follow‐up. Cumulative time‐dependent probabilities of seizure recurrence were calculated using Kaplan–Meier survival analysis. Logistic regression identified variables associated with seizure recurrence following ASM taper. Results: Eighty‐nine patients with a median age of 16 years were included, constituting 31% of those diagnosed with an idiopathic generalized epilepsy. Regarding the circadian distribution of seizures, 59.6% of patients exclusively experienced diurnal seizures, 12.4% exclusively nocturnal, and 28.1% experienced both diurnal and nocturnal seizures. Generalized spike–wave discharges (GSWD) were present in the initial EEG of 88% of patients. A GTC recurred in 14% of patients treated with ASM compared with 73% of untreated patients (p < 0.00001). ASM discontinuation was attempted in 50 patients after a median treatment duration of 3 years, with 44% experiencing a recurrence. Patient‐initiated taper and a mixed circadian seizure pattern independently predicted a higher likelihood of recurrence post‐ASM discontinuation. Significance: Our findings underscore the importance of prompt treatment upon the diagnosis of EGTCA. Notably, lifelong treatment may not be imperative; patients seizure‐free for at least 2 years, with the absence of GSWD on EEG, often maintained seizure freedom after ASM withdrawal, especially with physician‐initiated tapering. Plain Language Summary: Seizures in individuals diagnosed with "epilepsy with generalized tonic‐clonic seizures alone" (EGTCA) typically start during adolescence and often respond well to antiseizure medications. An electroencephalogram, which measure brain waves, will show abnormal discharges in most patients with EGTCA. Lifelong treatment with antiseizure medication is not necessary for everyone with EGTCA; approximately, 40% can successfully stop treatment without facing seizure recurrence. Patients who stop medication on their own have a higher risk of seizures returning compared with those who undergo cessation under a doctor's supervision. [ABSTRACT FROM AUTHOR]

Abstract Objective We evaluated huperzine A treatment in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) model of genetic generalized epilepsy (GGE) with absence seizures. Methods Adult male GAERS (N = 15) were implanted with EEG recording electrodes 10 days before receiving study drug. Each animal received the following six treatments as a single, intraperitoneal dose, 7 days apart (in random order): huperzine A (0.3, 1.0, or 3.0 mg/kg), two periods of vehicle (0.9% NaCl), or ethosuximide (100 mg/kg) as a positive control. Electroencephalograms (EEGs) were acquired for 24 h before and after each treatment and analyzed for seizure activity during the 90‐min period immediately post‐treatment, including 30‐min intervals at 30, 60, and 90 min. Additional analyses evaluated seizure activity over the 24‐h post‐treatment period using 60‐min intervals at 6, 12, and 24 h. The cumulative 24‐h periods before and after each administered treatment were also compared. Results Two‐way ANOVA showed a treatment difference [F(91,182) = 3.592, p

Abstract Objective This prospective study aimed to delineate the demographics, natural progression, and treatment response of patients newly diagnosed with epilepsy with generalized tonic–clonic seizures alone (EGTCA). Furthermore, our objective includes assessing the seizure recurrence rate post antiseizure medication (ASM) discontinuation within this cohort, alongside exploring predictive factors for seizure relapse. Methods The study cohort, derived from an ongoing, prospective, multicenter investigation on children and adults with new‐onset unprovoked seizures, included consecutive patients enrolled between March 2010 and March 2020, and meeting mandatory ILAE criteria for EGTCA diagnosis. Participants underwent a 3‐h sleep‐deprived video‐EEG recording along with an epilepsy protocol brain magnetic resonance imaging (MRI) with repeat EEG at each follow‐up. Cumulative time‐dependent probabilities of seizure recurrence were calculated using Kaplan–Meier survival analysis. Logistic regression identified variables associated with seizure recurrence following ASM taper. Results Eighty‐nine patients with a median age of 16 years were included, constituting 31% of those diagnosed with an idiopathic generalized epilepsy. Regarding the circadian distribution of seizures, 59.6% of patients exclusively experienced diurnal seizures, 12.4% exclusively nocturnal, and 28.1% experienced both diurnal and nocturnal seizures. Generalized spike–wave discharges (GSWD) were present in the initial EEG of 88% of patients. A GTC recurred in 14% of patients treated with ASM compared with 73% of untreated patients (p

The white matter (WM) functional network changes offers insights into the potential pathological mechanisms of certain diseases, the alterations of WM functional network in idiopathic generalized epilepsy (IGE) remain unclear. We aimed to explore the topological characteristics changes of WM functional network in childhood IGE using resting-state functional Magnetic resonance imaging (MRI) and T 1 -weighted images. A total of 84 children (42 IGE and 42 matched healthy controls) were included in this study. Functional and structural MRI data were acquired to construct a WM functional network. Group differences in the global and regional topological characteristics were assessed by graph theory and the correlations with clinical and neuropsychological scores were analyzed. A support vector machine algorithm model was employed to classify individuals with IGE using WM functional connectivity as features, and the model's accuracy was evaluated using leave-one-out cross-validation. In IGE group, at the network level, the WM functional network exhibited increased assortativity; at the nodal level, 17 nodes presented nodal disturbances in WM functional network, and nodal disturbances of 11 nodes were correlated with cognitive performance scores, disease duration and age of onset. The classification model achieved the 72.6% accuracy, 0.746 area under the curve, 69.1% sensitivity, 76.2% specificity. Our study demonstrated that the WM functional network topological properties changes in childhood IGE, which were associated with cognitive function, and WM functional network may help clinical classification for childhood IGE. These findings provide novel information for understanding the pathogenesis of IGE and suggest that the WM function network might be qualified as potential biomarkers. [ABSTRACT FROM AUTHOR]

Background: The clinical presentation of juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic–clonic seizures alone (GTCA) is similar, and MRI scans are often perceptually normal in both conditions making them challenging to differentiate. Purpose: To develop and validate an MRI‐based radiomics model to accurately diagnose JME and GTCA, as well as to classify prognostic groups. Study Type: Retrospective. Population: 164 patients (127 with JME and 37 with GTCA) patients (age 24.0 ± 9.6; 50% male), divided into training (n = 114) and test (n = 50) sets in a 7:3 ratio with the same proportion of JME and GTCA patients kept in both sets. Field Strength/Sequence: 3T; 3D T1‐weighted spoiled gradient‐echo. Assessment: A total of 17 region‐of‐interest in the brain were identified as having clinical evidence of association with JME and GTCA, from where 1581 radiomics features were extracted for each subject. Forty‐eight machine‐learning combinations of oversampling, feature selection, and classification algorithms were explored to develop an optimal radiomics model. The performance of the best radiomics models for diagnosis and for classification of the favorable outcome group were evaluated in the test set. Statistical Tests: Model performance measured using area under the curve (AUC) of receiver operating characteristic (ROC) curve. Shapley additive explanations (SHAP) analysis to estimate the contribution of each radiomics feature. Results: The AUC (95% confidence interval) of the best radiomics models for diagnosis and for classification of favorable outcome group were 0.767 (0.591–0.943) and 0.717 (0.563–0.871), respectively. SHAP analysis revealed that the first‐order and textural features of the caudate, cerebral white matter, thalamus proper, and putamen had the highest importance in the best radiomics model. Conclusion: The proposed MRI‐based radiomics model demonstrated the potential to diagnose JME and GTCA, as well as to classify prognostic groups. MRI regions associated with JME, such as the basal ganglia, thalamus, and cerebral white matter, appeared to be important for constructing radiomics models. Level of Evidence: 3 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

• Automated EEG software detected focal IEDs during long-term video EEG monitoring in all included patients with IGE (n = 32). • Almost a quarter of all detected IEDs showed a negative focal maximum. • Focal seizure symptoms were seen in three-quarter of IGE patients in our study. Focal seizure symptoms (FSS) and focal interictal epileptiform discharges (IEDs) are common in patients with idiopathic generalized epilepsies (IGEs), but dedicated studies systematically quantifying them both are lacking. We used automatic IED detection and localization algorithms and correlated these EEG findings with clinical FSS for the first time in IGE patients. 32 patients with IGEs undergoing long-term video EEG monitoring were systematically analyzed regarding focal vs. generalized IEDs using automatic IED detection and localization algorithms. Quantitative EEG findings were correlated with FSS. We observed FSS in 75% of patients, without significant differences between IGE subgroups. Mostly varying/shifting lateralizations of FSS across successive recorded seizures were seen. We detected a total of 81,949 IEDs, whereof 19,513 IEDs were focal (23.8%). Focal IEDs occurred in all patients (median 13% focal IEDs per patient, range 1.1 – 51.1%). Focal IED lateralization and localization predominance had no significant effect on FSS. All included patients with IGE showed focal IEDs and three-quarter had focal seizure symptoms irrespective of the specific IGE subgroup. Focal IED localization had no significant effect on lateralization and localization of FSS. Our findings may facilitate diagnostic and treatment decisions in patients with suspected IGE and focal signs. [ABSTRACT FROM AUTHOR]

While significant strides have been made in comprehending the pathophysiology and treatment of epilepsy, further investigation is warranted to elucidate the factors impacting its development and transmission, particularly within familial contexts. This study sought to explore the prevalence and risk factors associated with epilepsy in the offspring of patients with epilepsy who were treated at a tertiary epilepsy center. Adult patients with confirmed epilepsy (PWE) receiving outpatient care were consecutively enrolled, starting from January 2021 to January 2023. Data were recorded for various variables, including age, gender, epilepsy pathophysiology, cognitive impairment, and family history of epilepsy. Descriptive statistics, various statistical tests, and multivariate logistic regression analyses were employed to analyze the data. A total of 1456 PWE were included. Among them, 463 patients (31.8%) had children. Twenty-five patients had offspring diagnosed with epilepsy, representing a prevalence of 5.4%. Analysis of the offspring with epilepsy revealed older ages, a higher proportion of parents with idiopathic epilepsy, and a greater prevalence of a positive family history of epilepsy. Multivariate logistic regression analysis demonstrated a significant association between a family history of epilepsy and increased epilepsy risk in offspring. Genetic syndrome-immanent predisposition, advanced age, and a family history of epilepsy were identified as significant risk factors for epilepsy in offspring by means of this mono-center study. [ABSTRACT FROM AUTHOR]

• Déjà Vu is classically associated with focal seizures originating from the medial temporal lobe. • 3 % of Idiopathic Generalized Epilepsy patients reported Déjà Vu (ranging from 0 to 11 % in the studies). Any type of aura was reported by 40 %. • Clinicians should recognize that Déjà Vu and other auras may experienced in Idiopathic generalized Epilepsy. • Recognizing this pitfall is crucial to avoiding diagnostic and treatment errors. Déjà vu (DV), a French term meaning "already seen," refers to inappropriate sensation of familiarity in the present moment, as if it had been experienced before without a specific recollection of when or where. Traditionally, DV has been closely associated with focal seizures originating from the medial temporal lobe. However, there are occasional reports of DV occurring in idiopathic generalized epilepsies (IGEs). The objective of our study was to assess the presence and frequency of DV in individuals with IGE. We used the Preferred Reporting Items for Systematic Review and Meta-Analysis for protocols (PRISMA-P) and searched PubMed and Embase from January 2000 to July 2022. 5 studies were included with a total of 1177 IGE and 1026 with temporal lobe epilepsy (TLE) patients. The frequency of DV in IGE ranged from 0 to 11 %, and the average was 3 %, compared to 19.6 % in TLE. Broadly, 40 % of patients with IGE reported some type of aura. EEG correlation of DV in IGE was not appropriately evaluated in the studies. Clinicians should be aware that individuals with IGE may experience DV and other types of auras. Recognizing these auras is crucial in order to avoid misdiagnosing IGE as focal epilepsy. This is important to prevent unnecessary investigations and incorrect treatment decisions. [ABSTRACT FROM AUTHOR]

Generalized epilepsy affects 24 million people globally; at least 25% of cases remain medically refractory. The thalamus, with widespread connections throughout the brain, plays a critical role in generalized epilepsy. The intrinsic properties of thalamic neurons and the synaptic connections between populations of neurons in the nucleus reticularis thalami and thalamocortical relay nuclei help generate different firing patterns that influence brain states. In particular, transitions from tonic firing to highly synchronized burst firing mode in thalamic neurons can cause seizures that rapidly generalize and cause altered awareness and unconsciousness. Here, we review the most recent advances in our understanding of how thalamic activity is regulated and discuss the gaps in our understanding of the mechanisms of generalized epilepsy syndromes. Elucidating the role of the thalamus in generalized epilepsy syndromes may lead to new opportunities to better treat pharmaco-resistant generalized epilepsy by thalamic modulation and dietary therapy.

Idiopathic generalized epilepsy (IGE) is characterized by cryptogenic etiology and the striatum and cerebellum are recognized as modulators of epileptic network. We collected simultaneous electroencephalogram and functional magnetic resonance imaging data from 145 patients with IGE, 34 of whom recorded interictal epileptic discharges (IEDs) during scanning. In states without IEDs, hierarchical connectivity was performed to search core cortical regions which might be potentially modulated by striatum and cerebellum. Node–node and edge–edge moderation models were constructed to depict direct and indirect moderation effects in states with and without IEDs. Patients showed increased hierarchical connectivity with sensorimotor cortices (SMC) and decreased connectivity with regions in the default mode network (DMN). In the state without IEDs, striatum, cerebellum, and thalamus were linked to weaken the interactions of regions in the salience network (SN) with DMN and SMC. In periods with IEDs, overall increased moderation effects on the interaction between regions in SN and DMN, and between regions in DMN and SMC were observed. The thalamus and striatum were implicated in weakening interactions between regions in SN and SMC. The striatum and cerebellum moderated the cortical interaction among DMN, SN, and SMC in alliance with the thalamus, contributing to the dysfunction in states with and without IEDs in IGE. The current work revealed state-specific modulation effects of striatum and cerebellum on thalamocortical circuits and uncovered the potential core cortical targets which might contribute to develop new clinical neuromodulation techniques. [ABSTRACT FROM AUTHOR]

Epilepsy affects cognition through several mechanisms in a complex relationship. Valproic acid (VPA) and levetiracetam (LEV) are widely used due to their good efficacy and tolerability profiles. However, VPA may cause impairment of spatial working memory. There has not been much explanation regarding the negative cognitive side effects of LEV, few research suggests that LEV may even have a stimulating effect on cognition. Evidence of the comparative effects of anti-epileptic drugs on cognitive function is still limited. Objective: To investigate the effects of VPA monotherapy and LEV monotherapy on idiopathic generalized epilepsy patients. Methods: This was a cross-sectional observational study of patients with IGE taking either VPA monotherapy (n=28) or LEV (n=25). All patients underwent cognitive function assessment using MoCA-Ina, CDT, TMT A and B. Results: There was a significant association between 64.3% of patients taking VPA having MoCA-Ina score <26 vs. only 12% in patients taking LEV (OR 13.2, 95% CI 3.150-56.309, p<0.001), 35.7% of patients taking VPA vs. 0% in patients taking LEV on TMT-A score (p<0,001), and 46.4% of patients taking VPA vs. 4% in patients taking LEV on TMT-B score (OR 20.80, 95% CI 2.462-175.696, p 0,001). Neither patients with VPA monotherapy nor LEV monotherapy was statistically significant in CDT score (57.1% vs 36%, OR 0.422, 95% CI 0.139-1.277, p 0.170). Conclusion: This study showed patients with VPA have lower cognitive function than LEV. Further studies on cognitive function in epilepsy are recommended to provide information to assist in efficient drug selection decision-making for patients. [ABSTRACT FROM AUTHOR]

The transmembrane α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPAR) regulatory proteins (TARPs), γ2 (stargazin), γ3, γ4, γ5, γ7, and γ8, are a family of proteins that regulate AMPAR trafficking, expression, and biophysical properties that could have a role in the development of absence seizures. Here, we evaluated the expression of TARPs and AMPARs across the development of epilepsy in the genetic absence epilepsy rats from Strasbourg (GAERS) model of idiopathic generalized epilepsy (IGE) with absence seizures. Pre‐epileptic (7‐day‐old), early epileptic (6‐week‐old), and chronically epileptic (16‐week‐old) GAERS, and age‐matched male nonepileptic control rats (NEC) were used. Electroencephalographic (EEG) recordings were acquired from the 6‐ and 16‐week‐old animals to quantify seizure expression. Somatosensory cortex (SCx) and whole thalamus were collected from all the animals to evaluate TARP and AMPAR mRNA expression. Analysis of the EEG demonstrated a gradual increase in the number and duration of seizures across GAERS development. mRNA expression of the TARPs γ2, γ3, γ4, γ5, and γ8 in the SCx, and γ4 and γ5 in the thalamus, increased as the seizures started and progressed in the GAERS compared to NEC. There was a temporal association between increased TARP expression and seizures in GAERS, highlighting TARPs as potential targets for developing novel treatments for IGE with absence seizures. [ABSTRACT FROM AUTHOR]

The interaction between cerebellum and cerebrum participates widely in function from motor processing to high‐level cognitive and affective processing. Because of the motor symptom, idiopathic generalized epilepsy (IGE) patients with generalized tonic–clonic seizure have been recognized to associate with motor abnormalities, but the functional interaction in the cerebello–cerebral circuit is still poorly understood. Resting‐state functional magnetic resonance imaging data were collected for 101 IGE patients and 106 healthy controls. The voxel‐based functional connectivity (FC) between cerebral cortex and the cerebellum was contacted. The functional gradient and independent components analysis were applied to evaluate cerebello–cerebral functional integration on the voxel‐based FC. Cerebellar motor components were further linked to cerebellar gradient. Results revealed cerebellar motor functional modules were closely related to cerebral motor components. The altered mapping of cerebral motor components to cerebellum was observed in motor module in patients with IGE. In addition, patients also showed compression in cerebello–cerebral functional gradient between motor and cognition modules. Interestingly, the contribution of the motor components to the gradient was unbalanced between bilateral primary sensorimotor components in patients: the increase was observed in cerebellar cognitive module for the dominant hemisphere primary sensorimotor, but the decrease was found in the cerebellar cognitive module for the nondominant hemisphere primary sensorimotor. The present findings suggest that the cerebral primary motor system affects the hierarchical architecture of cerebellum, and substantially contributes to the functional integration evidence to understand the motor functional abnormality in IGE patients. [ABSTRACT FROM AUTHOR]

Recent morphometric magnetic resonance imaging (MRI) studies suggested the possibility that valproate (VPA) use is associated with parieto‐occipital cortical thinning in patients with heterogeneous epilepsy syndromes. In this study, we examined the effect of VPA on the brain volume using a large number of homogenous patients with idiopathic generalized epilepsy. Voxel‐based morphometry was used to compare regional gray matter (GM) volume between 112 patients currently taking VPA (VPA+ group), 81 patients not currently taking VPA (VPA– group), and 120 healthy subjects (control group). The VPA+ group showed a significant GM volume reduction in the bilateral cerebellum, hippocampus, insula, caudate nucleus, medial frontal cortex/anterior cingulate cortex, primary motor/premotor cortex, medial occipital cortex, and anteromedial thalamus, as compared to the control group. The VPA– group showed a significant GM volume reduction in the anteromedial thalamus and right hippocampus/temporal cortex, as compared to the control group. Compared to the VPA– group, the VPA+ group had a significant GM volume reduction in the bilateral cerebellum, primary motor/premotor cortex, and medial frontal cortex/anterior cingulate cortex. We have provided evidence that VPA use could result in GM volume reductions in the frontal cortex and cerebellum. Our findings should be acknowledged as a potential confounding factor in morphometric MRI studies that include subjects taking VPA. [ABSTRACT FROM AUTHOR]

Regular physical activity may promote beneficial neuroplasticity, e.g., increased hippocampus volume. However, it is unclear whether self-reported physical exercise in leisure (PEL) levels are associated with the brain structure features demonstrated by exercise interventions. This pilot study investigated the relationship between PEL, mood, cognition, and neuromorphometry in patients with idiopathic generalized epilepsy (IGEs) compared to healthy controls (HCs). Seventeen IGEs and 19 age- and sex-matched HCs underwent magnetic resonance imaging (MRI) at 3T. The Baecke Questionnaire of Habitual Physical Activity, Profile of Mood States, and Montreal Cognitive Assessment (MoCA) assessed PEL, mood, and cognition, respectively. Structural MRI data were analyzed by voxel- and surface-based morphometry. IGEs had significantly lower PEL (p

Objectives: To compare the efficacy and safety of antiseizure medications (ASMs), both as monotherapies and adjunctive therapies, for idiopathic generalized epilepsies (IGEs) and related entities. Methods: Two reviewers independently searched PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials from December 2022 to February 2023. Studies on the efficacy and safety of ASM monotherapies or adjunctive therapies for IGEs and related entities—including juvenile myoclonic epilepsy, childhood absence epilepsy (CAE), juvenile absence epilepsy, or generalized tonic–clonic seizures alone (GTCA)—were included. Efficacy outcomes were the proportions of patients remaining seizure free for 1, 3, 6, and 12 months; safety outcomes were the proportions of any treatment-emergent adverse event (TEAE) and TEAEs leading to discontinuation. Network meta-analyses were performed in a random-effects model to obtain odds ratios and 95% confidence intervals. Rankings of ASMs were based on the surface under the cumulative ranking curve (SUCRA). This study is registered with PROSPERO (No. CRD42022372358). Results: Twenty-eight randomized controlled trials containing 4282 patients were included. As monotherapies, all ASMs were more effective than placebo, and valproate and ethosuximide were significantly better than lamotrigine. According to the SUCRA for efficacy, ethosuximide ranked first for CAE, whereas valproate ranked first for other types of IGEs. As adjunctive therapies, topiramate ranked best for GTCA as well as overall for IGEs, while levetiracetam ranked best for myoclonic seizures. For safety, perampanel ranked best (measured by any TEAE). Conclusions: All of the studied ASMs were more effective than placebo. Valproate monotherapy ranked best overall for IGEs, whereas ethosuximide ranked best for CAE. Adjunctive topiramate and levetiracetam were most effective for GTCA and myoclonic seizures, respectively. Furthermore, perampanel had the best tolerability. [ABSTRACT FROM AUTHOR]

Background: With roughly 50 million people affected in the world, epilepsy is a particularly important disorder of the brain commonly diagnosed based on findings of quantitative electroencephalography (QEEG). The present investigation was aimed to evaluate differences in QEEG readings of drug-resistant and drug-responsive patients with idiopathic generalized epilepsy (IGE) with tonic-clonic seizures in a northwestern Iranian population.Methods: A total of 60 participants, consisting of 30 drug-resistant and 30 drug-responsive patients with IGE, were enrolled. Data, including demographic information and Z-transformed absolute power values of QEEG in anterior, central, and posterior alpha, beta, delta, and theta bands were collected. The analysis was conducted using IBM SPSS and a p-value

Objective:Cognitive impairment in patients with epilepsy appears as epileptic seizures or side effects of anti-seizure drugs (ASD). The aim of this study was to evaluate the cognitive functions of idiopathic generalized/genetic epilepsy (IGE) patients with digital neuropsychological tests (DNT) and to reveal whether there are differences in test batteries in patients using ASD with monotherapy or polytherapy.Methods:Thirty-nine individuals diagnosed with IGE syndrome in our clinic, who were diagnosed with IGE in the last decade and had completed at least eight years of education, were included in the study. After the Standardized Mini-Mental Test and Beck Depression Inventory, for neurocognitive evaluation, TestMyBrain (TMB) Number Range, TMB Selective Response Speed Test, TMB Visual Association Pairs Test, TMB Matrix Reasoning and TMB Number Symbol Matching Tests of TMB DNT Battery were applied to all participants.Results:Among the test categories in the current test battery that measure cognitive functionality in the areas of attention, short-term memory, working memory, visual memory, episodic memory, cognitive processing speed, selective response/inhibition, fluent cognitive skills and perceptual reasoning were applied to the patients and no significant difference was found between the groups receiving monotherapy or polytherapy (p

Abstract Background The thalamus is crucial in the development of idiopathic generalized epilepsy (IGE), which could lead to cognitive dysfunctions, according to data from neuropsychology and advanced neuroimaging investigations. This research aimed to measure the metabolic changes in the thalamus and to assess if could be contributed to cognitive impairment in IGE patients. Thirty IGE patients and thirty healthy volunteers with matched ages, genders, and educational levels participated in this cross-sectional case–control research. The IGE patients and controls were evaluated neuropsychologically using Intelligence Quotient (IQ) to assess general cognitive ability, Digit span for attention, Wechsler memory scale (WMS) for verbal memory, cube drawing test for visuospatial memory, Trail making test for executive functions, and Controlled Oral Word Association test (COWAT) for verbal fluency and quantitative multi-voxel MR spectroscopy (MRS) measurements of N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), NAA/Cr, NAA/Cho and Cho/Cr ratios at 1.5 T scanner. The voxels were located over the right and left thalamus. Results The IGE patients showed worse cognitive performance in IQ, attention, executive function, and verbal and visuospatial memory domains compared to the controls. The IGE patients exhibited a significantly decrease NAA in the right thalamus (p = 0.004) and a lower NAA/Cr ratio in the left thalamus (p = 0.01). the mean thalamus NAA level exhibited a positive correlation with CDT (r = 0.45, p = P = 0.01), and WMS-R (r = 0.39, p = 0.03) and a negative correlation with trail-making A test (r = 0.42, P = 0.01). Conclusions it was concluded that IGE patients exhibited poor cognition which could be attributed to thalamic neurometabolic changes due to impaired thalamic cortical circuits.

• Cognitive deficits are seen in all Idiopathic Generalized Epilepsies. • Cognitive deficits include executive dysfunction and reduced psychomotor speed. • Cognitive deficits are not associated with drug treatment outcome. The endophenotype of Idiopathic Generalized Epilepsies (IGE) comprises distinct neuropsychological deficits compared to normal controls. It is unknown if the severity of features of the endophenotype correlates with resistance to anti-seizure medication. Therefore, we here studied the association of neuropsychological profiles with treatment response. We evaluated 106 Danish patients aged ≥18 and diagnosed with IGE using a neuropsychological test battery comprising tests for executive dysfunction, visual attention, episodic memory, and verbal comprehension. Tests were complemented by the Purdue Pegboard test. Patients with suspected ongoing psychogenic non-epileptic seizures were excluded. At testing, 72 patients were seizure free, and 34 patients had recent seizures despite anti-seizure medication. As compared to age corrected Danish normative values, IGE patients showed significant impairments in semantic fluency and performed significantly worse in the Purdue Pegboard test. The vocabulary subtest of the WAIS-IV suggested lower verbal comprehension in IGE patients. We found no signs of memory impairment. Comparisons between results of the test battery, drug resistance, and the different IGE subsyndromes revealed consistent null-associations in various predefined and exploratory univariate and multivariate analyses. We here found and confirmed the distinct neuropsychological profile comprising impaired executive functions, reduced psychomotor speed, and normal memory previously described in juvenile myoclonic epilepsy. This profile was, however, not restricted to juvenile myoclonic epilepsy but equally affected all IGE patients. The neuropsychological deficits were not significantly associated with drug treatment outcome. [ABSTRACT FROM AUTHOR]

Gene sub-region encoded protein domain is the basic unit for protein structure and function. The DMD gene is the largest coding gene in humans, with its phenotype relevant to idiopathic generalized epilepsy. We hypothesized variants clustered in sub-regions of idiopathic generalized epilepsy genes and investigated the relationship between the DMD gene and idiopathic generalized epilepsy. Whole exome sequencing was performed in 106 idiopathic generalized epilepsy individuals. DMD variants were filtered with variant type, allele frequency, in silico prediction, hemizygous or homozygous status in the population, inheritance mode, and domain location. Variants located at the sub-regions were selected by the subRVIS software. The pathogenicity of variants was evaluated by the American College of Medical Genetics and Genomics criteria. Articles on functional studies related to epilepsy for variants clustered protein domains were reviewed. In sub-regions of the DMD gene, two variants were identified in two unrelated cases with juvenile absence epilepsy or juvenile myoclonic epilepsy. The pathogenicity of both variants was uncertain significance. Allele frequency of both variants in probands with idiopathic generalized epilepsy reached statistical significance compared with the population (Fisher's test, p = 2.02 × 10−6, adjusted α = 4.52 × 10−6). The variants clustered in the spectrin domain of dystrophin, which binds to glycoprotein complexes and indirectly affects ion channels contributing to epileptogenesis. Gene sub-region analysis suggests a weak association between the DMD gene and idiopathic generalized epilepsy. Functional analysis of gene sub-region helps infer the pathogenesis of idiopathic generalized epilepsy. [ABSTRACT FROM AUTHOR]

Abstract Background Epilepsy is a prevalent disease worldwide. Executive functions and social cognition are essential in daily living functioning, academic performance, and social adjustment. This study attempts to investigate the executive functions and ability to abstract social concepts in adolescents who have idiopathic generalized epilepsy and assess if the deterioration in executive functions can predict deterioration in the ability to abstract social concepts. Sixty adolescents with idiopathic generalized epilepsy aged between 12 and 19 collected from the neurology outpatient clinic at Sohag University Hospital in Upper Egypt were compared with 60 age- and sex-matched healthy adolescents regarding performance on executive function tests and ability to abstract social concepts tests. We used the Tower test to assess planning, the design fluency test to assess cognitive flexibility, the verbal fluency test to assess verbal fluency, and the Stroop test (overlapping between colour and word test) to assess inhibition and ability to abstract the social concepts test, which is composed of verbal part and performance part. Results Adolescents who have idiopathic generalized epilepsy have worse executive function impairment in all executive functions than control adolescents. Adolescents with idiopathic epilepsy have significantly more impairment in the ability to abstract social concepts (verbal and performance) compared to control adolescents. There is a significant correlation between executive functions and the ability to abstract social concepts (verbal and performance) in epileptic and control adolescents. Impairment in some executive functions can predict impairment in the ability to abstract social concepts (verbal and performance) in epileptic and control adolescents. Executive function impairment is correlated with the duration of illness, frequency of seizures per year, time since last epileptic fit, and presence of interictal epileptic discharge in EEG in the patient group. Conclusions Executive functions and the ability to abstract social concepts are significantly impaired in adolescents who have idiopathic generalized epilepsy. Impairment in executive functions can predict impairment in the ability to abstract social concepts. There is a need to screen executive functions and social abilities of adolescents with epilepsy and programmes to enhance these abilities.

Background: The thalamus is crucial in the development of idiopathic generalized epilepsy (IGE), which could lead to cognitive dysfunctions, according to data from neuropsychology and advanced neuroimaging investigations. This research aimed to measure the metabolic changes in the thalamus and to assess if could be contributed to cognitive impairment in IGE patients. Thirty IGE patients and thirty healthy volunteers with matched ages, genders, and educational levels participated in this cross-sectional case–control research. The IGE patients and controls were evaluated neuropsychologically using Intelligence Quotient (IQ) to assess general cognitive ability, Digit span for attention, Wechsler memory scale (WMS) for verbal memory, cube drawing test for visuospatial memory, Trail making test for executive functions, and Controlled Oral Word Association test (COWAT) for verbal fluency and quantitative multi-voxel MR spectroscopy (MRS) measurements of N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), NAA/Cr, NAA/Cho and Cho/Cr ratios at 1.5 T scanner. The voxels were located over the right and left thalamus. Results: The IGE patients showed worse cognitive performance in IQ, attention, executive function, and verbal and visuospatial memory domains compared to the controls. The IGE patients exhibited a significantly decrease NAA in the right thalamus (p = 0.004) and a lower NAA/Cr ratio in the left thalamus (p = 0.01). the mean thalamus NAA level exhibited a positive correlation with CDT (r = 0.45, p = P = 0.01), and WMS-R (r = 0.39, p = 0.03) and a negative correlation with trail-making A test (r = 0.42, P = 0.01). Conclusions: it was concluded that IGE patients exhibited poor cognition which could be attributed to thalamic neurometabolic changes due to impaired thalamic cortical circuits. [ABSTRACT FROM AUTHOR]

Objectives: Despite the prevalence of cognitive symptoms in the idiopathic generalized epilepsies (IGEs), cognitive dysfunction in juvenile absence epilepsy (JAE), a common yet understudied IGE subtype, remains poorly understood. This descriptive study provides a novel, comprehensive characterization of cognitive functioning in a JAE sample and examines the relationship between cognition and 24‐h epileptiform discharge load. Method: Forty‐four individuals diagnosed with JAE underwent cognitive assessment using Woodcock Johnson III Test of Cognitive Abilities with concurrent 24‐h ambulatory EEG monitoring. Generalized epileptiform discharges of any length, and prolonged generalized discharges ≥3 s were quantified across wakefulness and sleep. The relationship between standardized cognitive scores and epileptiform discharges was assessed through regression models. Results: Cognitive performances in overall intellectual ability, acquired comprehension‐knowledge, processing speed, long‐term memory storage and retrieval, and executive processes were 0.63–1.07 standard deviation (SD) units lower in the JAE group compared to the population reference mean, adjusted for educational attainment. Prolonged discharges (≥3 s) were recorded in 20 patients (47.6%) from 42 available electroencephalography (EEG) studies and were largely unreported. Duration and number of prolonged discharges were associated with reduced processing speed and long‐term memory storage and retrieval. Significance: Cognitive dysfunction is seen in patients with JAE across various cognitive abilities, including those representing more stable processes like general intellect. During 24‐h EEG, prolonged epileptiform discharges are common yet underreported in JAE despite treatment, and they show moderate effects on cognitive abilities. If epileptiform burden is a modifiable predictor of cognitive dysfunction, therapeutic interventions should consider quantitative 24‐h EEG with routine neuropsychological screening. The growing recognition of the spectrum of neuropsychological comorbidities of IGE highlights the value of multidisciplinary approaches to explore the causes and consequences of cognitive deficits in epilepsy. [ABSTRACT FROM AUTHOR]

Aims: Alterations in neuronal activity and cerebral hemodynamics have been reported in idiopathic generalized epilepsy (IGE) patients, possibly resulting in neurovascular decoupling; however, no neuroimaging evidence confirmed this disruption. This study aimed to investigate the possible presence of neurovascular decoupling and its clinical implications in childhood IGE using resting‐state fMRI and arterial spin labeling imaging. Methods: IGE patients and healthy participants underwent resting‐state fMRI and arterial spin labeling imaging to calculate degree centrality (DC) and cerebral blood flow (CBF), respectively. Across‐voxel CBF‐DC correlations were analyzed to evaluate the neurovascular coupling within the whole gray matter, and the regional coupling of brain region was assessed with the CBF/DC ratio. Results: The study included 26 children with IGE and 35 sex‐ and age‐matched healthy controls (HCs). Compared with the HCs, the IGE group presented lower across‐voxel CBF‐DC correlations, higher CBF/DC ratio in the right posterior cingulate cortex/precuneus, middle frontal gyrus, and medial frontal gyrus (MFG), and lower ratio in the left inferior frontal gyrus. The increased CBF/DC ratio in the right MFG was correlated with lower performance intelligence quotient scores in the IGE group. Conclusion: Children with IGE present altered neurovascular coupling, associated with lower performance intelligence quotient scores. The study shed a new insight into the pathophysiology of epilepsy and provided potential imaging biomarkers of cognitive performances in children with IGE. [ABSTRACT FROM AUTHOR]

Objective: Cognitive impairment in patients with epilepsy appears as epileptic seizures or side effects of anti-seizure drugs (ASD). The aim of this study was to evaluate the cognitive functions of idiopathic generalized/genetic epilepsy (IGE) patients with digital neuropsychological tests (DNT) and to reveal whether there are differences in test batteries in patients using ASD with monotherapy or polytherapy. Methods: Thirty-nine individuals diagnosed with IGE syndrome in our clinic, who were diagnosed with IGE in the last decade and had completed at least eight years of education, were included in the study. After the Standardized Mini-Mental Test and Beck Depression Inventory, for neurocognitive evaluation, TestMyBrain (TMB) Number Range, TMB Selective Response Speed Test, TMB Visual Association Pairs Test, TMB Matrix Reasoning and TMB Number Symbol Matching Tests of TMB DNT Battery were applied to all participants. Results: Among the test categories in the current test battery that measure cognitive functionality in the areas of attention, short-term memory, working memory, visual memory, episodic memory, cognitive processing speed, selective response/inhibition, fluent cognitive skills and perceptual reasoning were applied to the patients and no significant difference was found between the groups receiving monotherapy or polytherapy (p<0.05). Conclusion: It was concluded that the performance status of IGE patients in the sub-category tests included in the TMB DNT Battery and evaluated according to visual material was independent of the number of drugs, but this situation could not be independent of education. [ABSTRACT FROM AUTHOR]

Objective: Epilepsy with eyelid myoclonia (EEM) has been associated with marked clinical heterogeneity. Early epilepsy onset has been recently linked to lower chances of achieving sustained remission and to a less favorable neuropsychiatric outcome. However, much work is still needed to better delineate this epilepsy syndrome. Methods: In this multicenter retrospective cohort study, we included 267 EEM patients from nine countries. Data on electroclinical and demographic features, intellectual functioning, migraine with or without aura, family history of epilepsy, and epilepsy syndromes in relatives were collected in each patient. The impact of age at epilepsy onset (AEO) on EEM clinical features was investigated, along with the distinctive clinical characteristics of patients showing sporadic myoclonia involving body regions other than eyelids (body‐MYO). Results: Kernel density estimation revealed a trimodal distribution of AEO, and Fisher–Jenks optimization disclosed three EEM subgroups: early onset (EO‐EEM), intermediate onset (IO‐EEM), and late onset (LO‐EEM). EO‐EEM was associated with the highest rate of intellectual disability, antiseizure medication refractoriness, and psychiatric comorbidities and with the lowest rate of family history of epilepsy. LO‐EEM was associated with the highest proportion of body‐MYO and generalized tonic–clonic seizures (GTCS), whereas IO‐EEM had the lowest observed rate of additional findings. A family history of EEM was significantly more frequent in IO‐EEM and LO‐EEM compared with EO‐EEM. In the subset of patients with body‐MYO (58/267), we observed a significantly higher rate of migraine and GTCS but no relevant differences in other electroclinical features and seizure outcome. Significance: Based on AEO, we identified consistent EEM subtypes characterized by distinct electroclinical and familial features. Our observations shed new light on the spectrum of clinical features of this generalized epilepsy syndrome and may help clinicians toward a more accurate classification and prognostic profiling of EEM patients. [ABSTRACT FROM AUTHOR]

Although approximately 10%–15% of patients with idiopathic generalized epilepsy (IGE)/genetic generalized epilepsy remain drug‐resistant, there is no consensus or established concept regarding the underlying mechanisms and prevalence. This review summarizes the recent data and the current hypotheses on mechanisms that may contribute to drug‐resistant IGE. A literature search was conducted in PubMed and Embase for studies on mechanisms of drug resistance published since 1980. The literature shows neither consensus on the definition nor a widely accepted model to explain drug resistance in IGE or one of its subsyndromes. Large‐scale genetic studies have failed to identify distinct genetic causes or affected genes involved in pharmacokinetics. We found clinical and experimental evidence in support of four hypotheses: (1) "network hypothesis"—the degree of drug resistance in IGE reflects the severity of cortical network alterations, (2) "minor focal lesion in a predisposed brain hypothesis"—minor cortical lesions are important for drug resistance, (3) "interneuron hypothesis"—impaired functioning of γ‐aminobutyric acidergic interneurons contributes to drug resistance, and (4) "changes in drug kinetics"—genetically impaired kinetics of antiseizure medication (ASM) reduce the effectiveness of available ASMs. In summary, the exact definition and cause of drug resistance in IGE is unknown. However, published evidence suggests four different mechanisms that may warrant further investigation. [ABSTRACT FROM AUTHOR]

Magnus Spangsberg Boesen,1 Melita Cacic Hribljan,2 Søren Kirchhoff Christensen,1 Amalie Wandel Klein-Petersen,3 Sahla El Mahdaoui,4 Malini Vendela Sagar,5 Emilie Schou,5 Anna Korsgaard Eltvedt,6 Malene Landbo Børresen,3,7 Maria Jose Miranda,6 Alfred Peter Born,3 Peter Vilhelm Uldall,3 Lau Caspar Thygesen8 1Department of Neurology, Zealand University Hospital, Roskilde, Region Zealand, Denmark; 2Department of Clinical Neurophysiology, Copenhagen University Hospital, Copenhagen, Capital Region, Denmark; 3Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Copenhagen, Capital Region, Denmark; 4Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University Hospital, Glostrup, Capital Region, Denmark; 5Department of Neurology, Copenhagen University Hospital, Copenhagen, Capital Region, Denmark; 6Department of Paediatrics, Herlev Hospital, Herlev, Capital Region, Denmark; 7Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Capital Region, Denmark; 8National Institute of Public Health, University of Southern Denmark, Copenhagen, Capital Region, DenmarkCorrespondence: Magnus Spangsberg Boesen, Department of Neurology, Zealand University Hospital, Sygehusvej 10, Roskilde, 4000, Denmark, Tel +45 27634945, Email magnus.spangsberg.boesen@regionh.dkObjective: To identify pediatric idiopathic generalized epilepsy (IGE) during 1994– 2019 using ICD-10 codes in the Danish National Patient Register and anti-seizure prescriptions in the Danish Prescription Database.Study Design and Setting: We reviewed the medical records in children with ICD-10 codes for IGE before 18 years of age, and pediatric neurologists confirmed that the International League Against Epilepsy criteria were met. We estimated positive predictive values (PPV) and sensitivity for ICD-10 alone, including combinations of codes, anti-seizure prescription, and age at first code registration using medical record-validated diagnoses as gold standard.Results: We validated the medical record in 969 children with an ICD-10 code of IGE, and 431 children had IGE (115 childhood absence epilepsy, 97 juvenile absence epilepsy, 192 juvenile myoclonic epilepsy, 27 generalized tonic-clonic seizures alone). By combining ICD-10 codes with antiseizure prescription and age at epilepsy code registration, we found a PPV for childhood absence epilepsy at 44% (95% confidence interval [CI]=34%‒54%) and for juvenile absence epilepsy at 44% (95% CI=36%– 52%). However, ethosuximide prescription, age at ethosuximide code registration before age 8 years and a combination of ICD-10 codes yielded a PPV of 59% (95% CI=42%‒75%) for childhood absence epilepsy but the sensitivity was only 17% (20/115 children identified). For juvenile myoclonic epilepsy the highest PPV was 68% (95% CI=62%‒74%) using the code G40.3F plus antiseizure prescription and age at epilepsy code registration after age 8 years, with sensitivity of 85% (164/192 children identified). For generalized tonic-clonic seizures alone the highest PPV was 31% (95% CI=15%‒51%) using G40.3G during 2006– 2019 plus antiseizure prescription and age at code registration after age 5 years.Conclusion: The Danish National Patient Register and the Danish Prescription Database are not suitable for identifying children with IGE subtypes, except for juvenile myoclonic epilepsy which can be identified with caution.Keywords: idiopathic generalized epilepsy, register, ICD-10, validation, epilepsy

Idiopathic generalized epilepsies (IGEs) are a group of epilepsies characterized by an underlying genetic predisposition and a good response to antiseizure medicines (ASMs) in the majority of the patients. Of the various broad-spectrum ASMs, valproate is the most effective medicine for the control of seizures in IGEs. However, with the availability of many newer ASMs and evidence showing the high teratogenic potential of valproate, the choice of ASMs for IGEs has become increasingly difficult, especially in women of the child-bearing age group. In this article, we review the current evidence regarding the efficacy and safety of various ASMs in patients with IGEs and provide practical guidelines for choosing appropriate ASMs in various subgroups of patients with IGEs.

Background. Idiopathic generalized epilepsy (IGE) comprises 15–20% among all types of epilepsy. However, specifics of administration for lamotrigine in IGE in the Russian Federation remain poorly investigated, especially in female subjects.Objective: to assess efficacy and potential adverse events (AEs) in girls and females with preserved childbearing potential and verified IGE upon initial treatment with lamotrigine, upon switching to lamotrigine from a first-antiepileptic drug (AED) that provided no full seizure control and/or was coupled to AEs, as well as while introducing lamotrigine as an adjunctive therapy in case a monotherapy achieved no therapeutic efficacy.Material and methods. There were enrolled 54 female patients aged 4 to 40 years (mean age 19.3 years, median 11 years). After verifying IGE, patients received a monotherapy with lamotrigine. In case a patient received a first monotherapy course, but achieved no full seizure control and/or was coupled to AEs due to administered AED, lamotrigine was prescribed as a second AED followed by a potential for further switch to a second monotherapy.Results. It was found that a first monotherapy resulted in the maximum remission rate in patients with isolated generalized tonic-clonic seizures. Lamotrigine efficiently suppressed EEG epiactivity, with observed EEG-remission in 8 out of 16 (50%) patients. While being administered as a second monotherapy, lamotrigine resulted in remission in 87.5% patients. A combination therapy with lamotrigine was required in 22 cases. Most commonly, it was combined with levetiracetam (15 patients). While administering a dual therapy with lamotrigine, remission was observed in 9 patients receiving basal therapy with this drug, as well as 3 and 1 patients receiving valproic acid and topiramate, respectively. Six more patients were observed to demonstrate more than 50% improvement (5 subjects in levetiracetam group and 1 in ethosuximide group).Conclusions. The study demonstrated high efficacy of administered lamotrigine as a first monotherapy as well as a second monotherapy and a combination therapy in girls, adolescent girls and females with IGE. Lamotrigine resulted in no serious AEs that might lead to its cancellation.

Purpose: In patients with epilepsy (PWE), cognitive and behavioural dysfunctions are associated with abnormalities in various brain areas. The aim of the study was to compare the volume of the hippocampus (VHIP), amygdala (VAMG) and parahippocampal gyrus (VPHG) with the results of neuropsychological assessment in patients with temporal lobe epilepsy (TLE) and genetic generalized epilepsy (GGE). Methods: 33 PWE were enrolled in the study (mean age 37.3), 10 with TLE and 23 GGE (12 with GGE with tonic-clonic seizure [GGE-GTCS], and 11 with juvenile myoclonic epilepsy). 19 healthy persons (mean age 32.2) were enrolled as the control group (CG). Measurements of VHIP, VAMG and VPHG were made with 3D completely balanced steady state (CBASS) and 3D T1-weighted sequence. All participants underwent a neuropsychological assessment using a multi-domain cognitive battery and emotional state questionnaires. Results: The left hippocampus was significantly smaller in patients with left TLE (LTLE) and with GGE-GTCS, compared to the CG (p = 0.0069). In LTLE a significant enlargement of the right amygdala in comparison to the CG and other types of epilepsy were found (p = 0.0015). Among patients with LTLE and GGE-GTCS, impairment of attention and executive functions was statistically more common than in the CG. VHIP right (r = 0.25 p < 0.01) and VHIP left (r = 0.26 p < 0.04) were positively correlated with phonetic verbal fluency. Conclusions: PWE showed changes in the volume of selected medial temporal lobe (MTL) structures. Selective impairment of attention and executive functions was found. Some neuropsychological findings correlate with volume changes in MTL structures. Antiseizure medications therapy could have an impact on the severity of neuropsychological dysfunctions. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is a prevalent disease worldwide. Executive functions and social cognition are essential in daily living functioning, academic performance, and social adjustment. This study attempts to investigate the executive functions and ability to abstract social concepts in adolescents who have idiopathic generalized epilepsy and assess if the deterioration in executive functions can predict deterioration in the ability to abstract social concepts. Sixty adolescents with idiopathic generalized epilepsy aged between 12 and 19 collected from the neurology outpatient clinic at Sohag University Hospital in Upper Egypt were compared with 60 age- and sex-matched healthy adolescents regarding performance on executive function tests and ability to abstract social concepts tests. We used the Tower test to assess planning, the design fluency test to assess cognitive flexibility, the verbal fluency test to assess verbal fluency, and the Stroop test (overlapping between colour and word test) to assess inhibition and ability to abstract the social concepts test, which is composed of verbal part and performance part. Results: Adolescents who have idiopathic generalized epilepsy have worse executive function impairment in all executive functions than control adolescents. Adolescents with idiopathic epilepsy have significantly more impairment in the ability to abstract social concepts (verbal and performance) compared to control adolescents. There is a significant correlation between executive functions and the ability to abstract social concepts (verbal and performance) in epileptic and control adolescents. Impairment in some executive functions can predict impairment in the ability to abstract social concepts (verbal and performance) in epileptic and control adolescents. Executive function impairment is correlated with the duration of illness, frequency of seizures per year, time since last epileptic fit, and presence of interictal epileptic discharge in EEG in the patient group. Conclusions: Executive functions and the ability to abstract social concepts are significantly impaired in adolescents who have idiopathic generalized epilepsy. Impairment in executive functions can predict impairment in the ability to abstract social concepts. There is a need to screen executive functions and social abilities of adolescents with epilepsy and programmes to enhance these abilities. [ABSTRACT FROM AUTHOR]

Idiopathic generalized epilepsy (IGE) is a common type of epilepsy and despite an increase in the number of available anti-seizure medications, approximately 20-30% of people with IGE continue to experience seizures despite adequate medication trials. Unlike focal epilepsy, resective surgery is not a viable treatment option for IGE; however, neuromodulation may be an effective surgical treatment for people with IGE. Thalamic stimulation through deep brain stimulation (DBS) and responsive neurostimulation (RNS) have been explored for the treatment of generalized and focal epilepsies. Although the data regarding DBS and RNS in IGE is limited to case reports and case series, the results of the published studies have been promising. The current manuscript will review the published literature of DBS and RNS within the centromedian nucleus of the thalamus for the treatment of IGE, as well as highlight an illustrative case. [ABSTRACT FROM AUTHOR]

Abstract Objective: To determine the significance of parental consanguinity as a risk factor for idiopathic generalized epilepsies. Study Design: Case control study. Place and Duration of Study: Outdoor Section of Pediatric Neurology department, The Children Hospital Lahore, from Jan to Dec 2015. Methodology: A total of 402 patients were included in the study with case to control ratio of 1:1. The 201 cases suffering from idiopathic generalized epilepsy were taken from Pediatric Neurology outdoor and 201 non epileptic patients were taken from general outdoor of The Children Hospital Lahore. All the information was taken on predesigned Profoma. Results: The percentage of parental consanguinity in case group was 74.1% as compared to 54.7% in control group. Family history of epilepsy among cases was high (24%) as compared to control (10%). The most common type of epilepsy was generalized tonic clonic (GTC) 90.5% with mean age of onset of 5.2 years. The calculated Odd ratio for family history of epilepsy was 2.7 (OR=2.7, CI= 95%, p

Idiopathic generalized epilepsy (IGE) is a common type of epilepsy and despite an increase in the number of available anti-seizure medications, approximately 20–30% of people with IGE continue to experience seizures despite adequate medication trials. Unlike focal epilepsy, resective surgery is not a viable treatment option for IGE; however, neuromodulation may be an effective surgical treatment for people with IGE. Thalamic stimulation through deep brain stimulation (DBS) and responsive neurostimulation (RNS) have been explored for the treatment of generalized and focal epilepsies. Although the data regarding DBS and RNS in IGE is limited to case reports and case series, the results of the published studies have been promising. The current manuscript will review the published literature of DBS and RNS within the centromedian nucleus of the thalamus for the treatment of IGE, as well as highlight an illustrative case.

Idiopathic generalized epilepsy (IGE) was characterized by 3–6 Hz generalized spikewave discharges (GSWDs), and extensive altered interactions in subcortical-cortical circuit. However, the dynamics and the causal relationship among these interactions were less studied. Using resting-state functional magnetic resonance imaging (fMRI) data, the abnormal connections in the subcortical-cortical pathway in IGE were examined. Then, we proposed a novel method of granger causal analysis based on the dynamic functional connectivity, and the predictive effects among these abnormal connections were calculated. The results showed that the thalamus, and precuneus were key regions representing abnormal functional network connectivity (FNC) in the subcortical-cortical circuit. Moreover, the connectivity between precuneus and adjacent regions had a causal effect on the widespread dysfunction of the thalamocortical circuit. In addition, the connection between the striatum and thalamus indicated the modulation role on the cortical connection in epilepsy. These results described the causality of the widespread abnormality of the subcortical-cortical circuit in IGE in terms of the dynamics of functional connections, which provided additional evidence for understanding the potential modulation pattern of the abnormal epileptic pathway. [ABSTRACT FROM AUTHOR]

Background: Studies have demonstrated that adults with idiopathic generalized epilepsy (IGE) have functional abnormalities; however, the neuropathological pathogenesis differs between adults and children. This study aimed to explore alterations in the cerebral blood flow (CBF) and functional connectivity (FC) to comprehensively elucidate the neuropathological mechanisms of IGE in children. Methods: We obtained arterial spin labeling (ASL) and resting state functional magnetic resonance imaging data of 28 children with IGE and 35 matched controls. We used ASL to determine differential CBF regions in children with IGE. A seed-based whole-brain FC analysis was performed for regions with significant CBF changes. The mean CBF and FC of brain areas with significant group differences was extracted, then its correlation with clinical variables in IGE group was analyzed by using Pearson correlation analysis. Results: Compared to controls, children with IGE had CBF abnormalities that were mainly observed in the right middle temporal gyrus, right middle occipital gyrus (MOG), right superior frontal gyrus (SFG), left inferior frontal gyrus (IFG), and triangular part of the left IFG (IFGtriang). We observed that the FC between the left IFGtriang and calcarine fissure (CAL) and that between the right MOG and bilateral CAL were decreased in children with IGE. The CBF in the right SFG was correlated with the age at IGE onset. FC in the left IFGtriang and left CAL was correlated with the IGE duration. Conclusion: This study found that CBF and FC were altered simultaneously in the left IFGtriang and right MOG of children with IGE. The combination of CBF and FC may provide additional information and insight regarding the pathophysiology of IGE from neuronal and vascular integration perspectives. [ABSTRACT FROM AUTHOR]

[Display omitted] • Different generalized tonic clonic seizure (GTCS) subtypes occur in various genetic generalized epilepsy syndromes and in individual patients. • At onset, GTCS subtypes activate similar brain regions but differ in long-range connectivity. • GTCS evolution to tonic-start epoch associates with reduced long-range connectivity, particularly at δ/θ frequencies. To determine EEG spatiospectral activation and connectivity in the generalized tonic-clonic seizure (GTCS) semiological subtypes. 39 patients with genetic generalized epilepsy (GGE) who had GTCS (n = 58) during video-EEG monitoring were identified in the Vanderbilt Epilepsy database. GTCSs were classified as absence tonic-clonic, myoclonic tonic-clonic, or tonic-clonic. Patient characteristics and semiological features were compared. Spectral power and node degree, a network measure of connectivity, were calculated at two seizure epochs, electrographic and tonic-start. Different GTCS subtypes occurred within individual patients. At electrographic-onset, all subtypes activated midline frontal cortex at delta/theta and beta frequencies but differed in network connectivity. In all subtypes, GTCS evolution from electrographic to tonic-start associated with preserved beta frequency spectral power, but reduced connectivity and delta/theta power. Our findings suggest that at GTCS onset, the subtypes activate similar cortical regions and their different initial semiologies relate to their distinct onset long-range connectivity. Upon transition to the tonic-start epoch, the ictal activity is predominantly conveyed by β frequency activity and connectivity. Future neurostimulation therapies for medically intractable GTCSs may target the same brain regions for all GTCS subtypes and may be most effective prior to the tonic-start epoch. [ABSTRACT FROM AUTHOR]

Epilepsy syndromes have been recognized for >50 years, as distinct electroclinical phenotypes with therapeutic and prognostic implications. Nonetheless, no formally accepted International League Against Epilepsy (ILAE) classification of epilepsy syndromes has existed. The ILAE Task Force on Nosology and Definitions was established to reach consensus regarding which entities fulfilled criteria for an epilepsy syndrome and to provide definitions for each syndrome. We defined an epilepsy syndrome as "a characteristic cluster of clinical and electroencephalographic features, often supported by specific etiological findings (structural, genetic, metabolic, immune, and infectious)." The diagnosis of a syndrome in an individual with epilepsy frequently carries prognostic and treatment implications. Syndromes often have age‐dependent presentations and a range of specific comorbidities. This paper describes the guiding principles and process for syndrome identification in both children and adults, and the template of clinical data included for each syndrome. We divided syndromes into typical age at onset, and further characterized them based on seizure and epilepsy types and association with developmental and/or epileptic encephalopathy or progressive neurological deterioration. Definitions for each specific syndrome are contained within the corresponding position papers. [ABSTRACT FROM AUTHOR]

There is a paucity of treatment options for cognitively normal individuals with drug resistant genetic generalized epilepsy (GGE). Centromedian nucleus of the thalamus (CM) deep brain stimulation (DBS) may be a viable treatment for GGE. Here, we present the case of a 27-year-old cognitively normal woman with drug resistant GGE, with childhood onset. Seizure semiology are absence seizures and generalized onset tonic clonic (GTC) seizures. At baseline she had 4–8 GTC seizures per month and weekly absence seizures despite three antiseizure medications and vagus nerve stimulation. A multidisciplinary committee recommended off-label use of CM DBS in this patient. Over 12-months of CM DBS she had two GTC seizure days, which were in the setting of medication withdrawal and illness, and no GTC seizures in the last 6 months. There was no significant change in the burden of absence seizures. Presently, just two studies clearly document CM DBS in cognitively normal individuals with GGE or idiopathic generalized epilepsy (IGE) [in contrast to studies of cognitively impaired individuals with developmental and epileptic encephalopathies (DEE)]. Our results suggest that CM DBS can be an effective treatment for cognitively normal individuals with GGE and underscore the need for prospective studies of CM DBS. [ABSTRACT FROM AUTHOR]

Most of the epileptic seizures that begin at an advanced age are focal onset seizures due to an underlying structural lesion. Generalized myoclonic seizures, usually seen in adolescence, are very rare in elderly patients without a history of epilepsy. In this study, we present a 60-year-old patient with generalized myoclonic seizures with electrophysiological findings. Because of the late-onset, myoclonic jerks were first evaluated with the diagnosis of non-epileptic psychogenic attack in an external health center. The patient was diagnosed with seizure recordings in Electroencephalography-video monitoring. The patient responded well to the antiepileptic treatment and became seizure-free.

BackgroundStudies have demonstrated that adults with idiopathic generalized epilepsy (IGE) have functional abnormalities; however, the neuropathological pathogenesis differs between adults and children. This study aimed to explore alterations in the cerebral blood flow (CBF) and functional connectivity (FC) to comprehensively elucidate the neuropathological mechanisms of IGE in children.MethodsWe obtained arterial spin labeling (ASL) and resting state functional magnetic resonance imaging data of 28 children with IGE and 35 matched controls. We used ASL to determine differential CBF regions in children with IGE. A seed-based whole-brain FC analysis was performed for regions with significant CBF changes. The mean CBF and FC of brain areas with significant group differences was extracted, then its correlation with clinical variables in IGE group was analyzed by using Pearson correlation analysis.ResultsCompared to controls, children with IGE had CBF abnormalities that were mainly observed in the right middle temporal gyrus, right middle occipital gyrus (MOG), right superior frontal gyrus (SFG), left inferior frontal gyrus (IFG), and triangular part of the left IFG (IFGtriang). We observed that the FC between the left IFGtriang and calcarine fissure (CAL) and that between the right MOG and bilateral CAL were decreased in children with IGE. The CBF in the right SFG was correlated with the age at IGE onset. FC in the left IFGtriang and left CAL was correlated with the IGE duration.ConclusionThis study found that CBF and FC were altered simultaneously in the left IFGtriang and right MOG of children with IGE. The combination of CBF and FC may provide additional information and insight regarding the pathophysiology of IGE from neuronal and vascular integration perspectives.

There is a paucity of treatment options for cognitively normal individuals with drug resistant genetic generalized epilepsy (GGE). Centromedian nucleus of the thalamus (CM) deep brain stimulation (DBS) may be a viable treatment for GGE. Here, we present the case of a 27-year-old cognitively normal woman with drug resistant GGE, with childhood onset. Seizure semiology are absence seizures and generalized onset tonic clonic (GTC) seizures. At baseline she had 4–8 GTC seizures per month and weekly absence seizures despite three antiseizure medications and vagus nerve stimulation. A multidisciplinary committee recommended off-label use of CM DBS in this patient. Over 12-months of CM DBS she had two GTC seizure days, which were in the setting of medication withdrawal and illness, and no GTC seizures in the last 6 months. There was no significant change in the burden of absence seizures. Presently, just two studies clearly document CM DBS in cognitively normal individuals with GGE or idiopathic generalized epilepsy (IGE) [in contrast to studies of cognitively impaired individuals with developmental and epileptic encephalopathies (DEE)]. Our results suggest that CM DBS can be an effective treatment for cognitively normal individuals with GGE and underscore the need for prospective studies of CM DBS.