Epilepsy Control Research Articles

Effect of Classic Ketogenic Diet Versus Modified Atkins Diet over Electro-Encephalogram Findings in Children with Refractory Epilepsy

ABSTRACT Introduction: Ketogenic diet (KD) is well known for control of refractory epilepsy. We wanted to study the effect of the two types of diets: classic KD and modified Atkins diet (MAD) with Indian foods to children of refractory epilepsy on electroencephalogram (EEG). Aim: To determine the effect of KD on EEG on children with refractory epilepsy. Material and Methods: Ethics Committee approval was taken for randomized controlled trials. Sixty-five children of refractory epilepsy of 6 months to 12 years’ age from two tertiary care teaching institutes, of Pune and Mumbai, were selected and allocated to one of the two types of diets, classic KD and MAD, and followed over a period of 6 months. EEG was done in the beginning, at 3 months, and at 6 months of completion of therapy with standard techniques. Observations: The relationship of EEG findings at 3 months follow-up was statistically non-significant, but at the end of 6 months, when overall improved activity on EEG was compared, it had a significant difference of P-value = 0.01, stating KD better than MAD. Conclusion: Classic KD is better than MAD.

Astrocyte switch to the hyperactive mode.

Increasing pieces of evidence have suggested that astrocyte function has a strong influence on neuronal activity and plasticity, both in physiological and pathophysiological situations. In epilepsy, astrocytes have been shown to respond to epileptic neuronal seizures; however, whether they can act as a trigger for seizures has not been determined. Here, using the copper implantation method, spontaneous neuronal hyperactivity episodes were reliably induced during the week following implantation. With near 24-h continuous recording for over 1 week of the local field potential with in vivo electrophysiology and astrocyte cytosolic Ca2+ with the fiber photometry method, spontaneous occurrences of seizure episodes were captured. Approximately 1 day after the implantation, isolated aberrant astrocyte Ca2+ events were often observed before they were accompanied by neuronal hyperactivity, suggesting the role of astrocytes in epileptogenesis. Within a single developed episode, astrocyte Ca2+ increase preceded the neuronal hyperactivity by ~20 s, suggesting that actions originating from astrocytes could be the trigger for the occurrence of epileptic seizures. Astrocyte-specific stimulation by channelrhodopsin-2 or deep-brain direct current stimulation was capable of inducing neuronal hyperactivity. Injection of an astrocyte-specific metabolic inhibitor, fluorocitrate, was able to significantly reduce the magnitude of spontaneously occurring neuronal hyperactivity. These results suggest that astrocytes have a role in triggering individual seizures and the reciprocal astrocyte-neuron interactions likely amplify and exacerbate seizures. Therefore, future epilepsy treatment could be targeted at astrocytes to achieve epilepsy control.

Clinical and genetic spectrum of 6 cases with asparagine synthetase deficiency

Objective: To explore the clinical and genetic characteristics of asparagine synthase deficiency. Methods: Case series studies. Retrospective analysis and summary of the clinical data of 6 cases with asparagine synthase deficiency who were diagnosed by genetic testing and admitted to the Third Affiliated Hospital of Zhengzhou University from May 2017 to April 2023 were analyzed retrospectively. The main clinical features, laboratory and imaging examination characteristics of the 6 cases were summarized, and the gene variation sites of them were analyzed. Results: All of the 6 cases were male, with onset ages ranging from 1 month to 1 year and 4 months. All of the 6 cases had cognitive and motor developmental delay, with 3 cases starting with developmental delay, 3 cases starting with convulsions and later experiencing developmental arrest or even regression. All of 6 cases had epilepsy, in whom 2 cases with severe microcephaly developed epileptic encephalopathy in the early stages of infancy with spasms as the main form of convulsions, 4 cases with mild or no microcephaly gradually evolved into convulsions with no fever after multiple febrile convulsions with focal seizures, tonic clonic seizures and tonic seizure as the main forms of convulsions. Three cases of 4 gradually developed into stagnation or even regression of development and ataxia after multiple convulsions with no fever. There were normal cranial imaging in 2 cases, dysplasia of the brains in 1 cases, frontal lobe apex accompanied by abnormal white matter signal in the frontal lobe and thin corpus callosum in 1 case, thin corpus callosum and abnormal lateral ventricular morphology in 1 case, and normal in early stage, but gradually developing into cerebellar atrophy at the age of 5 years and 9 months in 1 case. Two cases underwent visual evoked potential tests, the results of which were both abnormal. Three cases underwent auditory evoked potential examination, with 1 being normal and 2 being abnormal. All of 6 cases had variations in the asparagine synthase gene, with 2 deletion variations and 7 missense variations. The variations of 2 cases had not been reported so far, including c.1341_1343del and c.1283A>G, c.1165_1167del and c.1075G>A. The follow-up time ranged from 3 months to 53 months. Two cases who had severe microcephaly died in infancy, while the other 4 cases with mild or no microcephaly were in survival states until the follow-up days but the control of epilepsy was poor. Conclusions: Asparagine synthase deficiency has a certain degree of heterogeneity in clinical phenotype. Children with obvious microcephaly often present as severe cases, while children with mild or no microcephaly have relatively mild clinical manifestations. The variation of asparagine synthetase gene is mainly missense variation.

Efficacy and Safety of adjunctive Perampanel in a prospective, real-world, Phase IV study in Indian patients aged ≥12 years for Treatment of focal-onset Epilepsy: Study 508.

ESPRITE (Study 508; NCT03836924) evaluated the real-world safety, tolerability, and efficacy of adjunctive perampanel in patients aged ≥12 years with focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS), in India. ESPRITE was a prospective, multicenter, single-arm, observational, Phase IV study with a 6-month Treatment Period. Patients were aged ≥12 years and had been prescribed perampanel for adjunctive treatment of FOS, with or without FBTCS. Assessments included incidence of treatment-emergent adverse events (TEAEs; primary endpoint), median percent reduction in seizure frequency per 28 days from baseline, 50% responder rates, and seizure-freedom rates. Overall, 200 patients were enrolled (199 patients in the Safety Analysis Set and 174 patients who completed all visits in the main efficacy analyses). TEAEs (all mild or moderate in severity) were reported in 18.1% (n = 36/199) of patients (the most common were dizziness [3.0%] and irritability [2.0%]). TEAEs leading to discontinuation of perampanel were reported in 2.0% of patients; no deaths or serious TEAEs occurred. At 6 months, median percent reduction in seizure frequency was 100.0%, 50% responder rate was 83.3%, and seizure-freedom rate was 49.4%. Adjunctive perampanel (at a mean daily dose of 4 mg/day) was shown to be well tolerated and effective in patients aged ≥12 years with FOS, with or without FBTCS, from India. Many patients do not receive adequate treatment for epilepsy and need effective seizure control medications. In this 6-month clinical study, 199 patients from India, aged 12 years or older, added perampanel to the anti-seizure medications they were already taking. At 6 months, 49% of patients experienced no seizures since starting perampanel and seizure frequency was reduced by half in 83% of patients. Side effects occurred in 18% of patients (most commonly dizziness and irritability) and caused 2% to stop perampanel; no deaths were reported. Perampanel was an effective and generally safe added medication for patients with epilepsy from India.

A Study of Hippocampal T2 Relaxometry Value in Temporal Lobe Epilepsy Patient

In the advancement of the current imaging technique for detection of mesial temporal sclerosis in temporal lobe epilepsy patient, there are multiple Magnetic resonance imaging (MRI) quantitative techniques. One of the long known to be valuable quantitative technique is T2 relaxometry where it has overall better accuracy for detection of mesial temporal sclerosis compared with the qualitative assessment only. A comparative cross-sectional study was conducted in Hospital Universiti Sains Malaysia from August 2021 to January 2023 which include 51 participants, 19 (36.5%) were temporal lobe epilepsy patient and 33 (63.5%) were control. The hippocampal T2 relaxometry was calculated for temporal lobe epilepsy patient and control. The mean T2 relaxometry reading for these groups were compared using Independent T-test. The correlation of T2 relaxometry value with age, duration of epilepsy and seizure frequency were analysed using Pearson correlation. Cohen Kappa inter-rater reliability was done for MR qualitative assessment. The participant age range was from 15 to 65 years old. Total of 23 samples were male (44.2%). The mean T2 relaxometry for epilepsy patient was higher than control. For correlation, moderate to good positive correlation was seen between the duration of epilepsy with T2 relaxometry of right hippocampus. Whereas poor positive correlation between the right hippocampus T2 relaxometry with age (P>0.01), as well poor positive correlation between both hippocampus T2 relaxometry with seizure frequency (P>0.01). There was one patient (5.2%) reported to be negative for mesial temporal sclerosis by qualitative assessment, but the T2 relaxometry reading however was raised. As a conclusion, T2 relaxometry sequence can be use as adjunct to the current qualitative assessment to increase sensitivity and specificity in detecting mesial temporal sclerosis.
 Keywords: Temporal lobe epilepsy, Mesial temporal sclerosis, T2 relaxometry, MRI epilepsy protocol

Identification of genetic causes in children with unexplained epilepsy based on trio-whole exome sequencing.

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

Cognitive dysfunction at epilepsy onset as a marker for seizure recurrence

BackgroundCognitive dysfunction has been correlated with seizure control in chronic epilepsy and in newly diagnosed epilepsy, which potentially makes it a good marker for predicting disease course and seizure control. However, there is a lack of prospective studies examining the role of cognitive dysfunction in predicting seizure recurrence at the earliest stages of the disease, such as following the first unprovoked seizure (UFS) or new onset epilepsy (NOE). MethodsThirty three adult participants (FS=18, NOE=15) from the Halifax First Seizure Clinic (HFSC) completed a cognitive screening assessment at baseline (typically 3 months following diagnosis); seizure-recurrence was evaluated one year after the initial HFSC visit. ResultsCognitive impairment, defined as at least one z-score in the impaired range (≤-1.5) relative to published test norms, was documented in 76% of the patients with seizure recurrence at follow-up and in 55% without seizure recurrence. Speed/executive functions and Memory were the most frequently affected domains, with impaired performance noted in 35% and 29% of the entire sample, respectively. Although the seizure recurrence vs. non-recurrence groups did not differ significantly on likelihood of impairment in any specific cognitive domains, a regression model of seizure recurrence that included years of education, baseline mood and anxiety scores, normal vs. abnormal baseline MRI, and impaired (vs. unimpaired) function in six cognitive domains was significant overall (Χ2 (10) = 24.04, p =.007*, R2N =.77). The regression model was no longer significant with the cognitive variables removed. ConclusionsSubtle cognitive dysfunction, especially in the domains of executive functions and memory are prevalent in individuals at the earliest stages of epilepsy. In addition to abnormal MRI and EEG findings at baseline, which are far less prevalent in FS and NOE, cognitive factors show promise in helping predict seizure recurrence in these populations.

Established and emerging GABAA receptor pharmacotherapy for epilepsy.

Drugs that modulate the GABAA receptor are widely used in clinical practice for both the long-term management of epilepsy and emergency seizure control. In addition to older medications that have well-defined roles for the treatment of epilepsy, recent discoveries into the structure and function of the GABAA receptor have led to the development of newer compounds designed to maximise therapeutic benefit whilst minimising adverse effects, and whose position within the epilepsy pharmacologic armamentarium is still emerging. Drugs that modulate the GABAA receptor will remain a cornerstone of epilepsy management for the foreseeable future and, in this article, we provide an overview of the mechanisms and clinical efficacy of both established and emerging pharmacotherapies.

Effective treatment of NR2F1-related epilepsy with perampanel

BackgroundNR2F1 mutations are associated with Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS). Although ~ 46.7% of BBSOAS patients present with epilepsy, which is always drug-resistant and associated with higher rates of behavioral and cognitive problems, the treatment and outcomes of NR2F1-related epilepsy have rarely been described. Here, we present new cases of BBSOAS-related epilepsy and summarize all previously reported cases to explore the effective treatment for this type of epilepsy.MethodsWe identified six new Chinese cases of BBSOAS with epilepsy. Five different de novo heterozygous NR2F1 mutations were identified in these cases, including two novel mutations c.365G > T, p.Cys122Phe and c.449G > T, p.Gly150Val. By combining the six cases and 14 previously reported cases, we analyzed the characteristics and treatment outcomes of NR2F1-related epilepsy.ResultsTwelve of the 20 patients (60%) had infantile epileptic spasms, while the other patients had generalized tonic/tonic-clonic, focal, myoclonic, absence, or unclassified seizures. Several anti-seizure medications, steroids, and a ketogenic diet were administered in these cases. However, seizures were controlled in only 50% of previously reported cases, while all of the six new cases became seizure-free after perampanel as an add-on treatment. The average time from the addition of perampanel to seizure control was 7.33 ± 4.59 months (range, 1–12 months). The median time to seizure freedom was 14 months (1–32 months, > 19 months in 3 cases). The average dosage of perampanel needed for epilepsy control was 0.22 ± 0.17 mg/kg per day.ConclusionsIn this paper, we comprehensively summarized the clinical characteristics, treatments and outcomes of NR2F1-related epilepsy for the first time. Perampanel exhibits dramatic efficacy for NR2F1-related epilepsy. This will help optimize the treatment of this type of epilepsy and provide clues for its pathogenic mechanisms. The two novel mutations expand the genotype spectrum of this disease.

Depression and poor sleep: neglected prevalent issues among adult epileptic patients

BackgroundPsychiatric comorbidities, and sleep disorders, are prevalent in adults with epilepsy (AWE). Good control of epilepsy can help AWE lead a normal fruitful life and incorporate in daily activities as others. This study aims to assess the frequency, risk factors of depression, and poor sleep quality among patients with epilepsy and examine their relation with epilepsy control.MethodsThis cross-sectional study was accomplished during the period from January to October 2023 involving 179 AWE. All were exposed to complete history taking: stressing on personal data, evaluation of medication adherence using the modified Morisky scale, sleep quality using the Pittsburgh Sleep Quality Index, and depressive symptoms evaluated by the Zagazig Depression Scale.ResultsDepression was reported in 22.2% of studied patients; while 44.4% had poorer epilepsy control. Poor sleep quality was reported in 35.2% of epilepsy patients and was associated with non-adherence and poor seizure control. Depression increased the risk of poor control by about 16-folds. Non-adherence was associated with depression and poor sleep quality and was one of the predictors of poor epilepsy control.ConclusionDepression and poor sleep quality can impair the outcome of PWE and also there is a strong association between depression and poor sleep quality among PWE and both impair seizure control.

Altered functional connectivity in the hippocampal and striatal systems after motor sequence learning consolidation in medial temporal lobe epilepsy individuals.

Both the hippocampal and striatal systems participate in motor sequence learning (MSL) in healthy subjects, and the prominent role of the hippocampal system in sleep-related consolidation has been demonstrated. However, some pathological states may change the functional dominance between these two systems in MSL consolidation. To better understand the functional performance within these two systems under the pathological condition of hippocampal impairment, we compared the functional differences after consolidation between patients with left medial temporal lobe epilepsy (LmTLE) and healthy control subjects (HCs). We assessed participants' performance on the finger-tapping task (FTT) during acquisition (on day 1) and after consolidation during sleep (on day 2). All participants underwent an MRI scan (T1 and resting state) before each FTT. We found that the LmTLE group showed performance deficits in offline consolidation compared to the HC group. The LmTLE group exhibited structural changes, such as decreased gray matter volume (GMV) in the left hippocampus and increased GMV in the right putamen (striatum). Our results also revealed that whereas the main effect of consolidation was observed in the hippocampus-related functional connection in the HC group, it was only evident in the striatum-related functional loop in the LmTLE group. Our findings indicated that LmTLE patients may rely more on the striatal system for offline consolidation because of structural impairments in the hippocampus. Additionally, this compensatory mechanism may not fully substitute for the role of the impaired hippocampus itself.NEW & NOTEWORTHY Motor sequence learning (MSL) relies on both the hippocampal and striatal systems, but whether functional performance is altered after MSL consolidation when the hippocampus is impaired remains unknown. Our results indicated that whereas the main effect of consolidation was observed in the hippocampus-related functional connection in the healthy control (HC) group, it was only evident in the striatum-related functional loop in the left medial temporal lobe epilepsy (LmTLE) group.

The relationships between obesity and epilepsy: A systematic review with meta-analysis.

There is ongoing debate regarding the association between epilepsy and obesity. Thus, the aim of this study was to examine the correlation between epilepsy and obesity. This study adhered to the PRISMA guidelines for systematic reviews and meta-analyses. On The Prospero website, this study has been successfully registered (CRD42023439530), searching electronic databases from the Cochr-ane Library, PubMed, Web of Sciences and Embase until February 10, 2024.The search keywords included "Epilepsy", "Obesity", "Case-Control Studies", "cohort studies", "Randomized Controlled Trial" and "Cross-Sectional Studies". The medical subject headings(MeSH) of PubMed was utilized to search for relevant subject words and free words, and a comprehensive search strategy was developed. Two reviewers conducted article screening, data extraction and bias risk assessment in strict accordance with the predefined criteria for including and excluding studies. The predefined inclusion criteria were as follows: 1) Inclusion of case-control, cohort, randomized controlled trial, and cross-sectional studies; 2) Segregation of subjects into epileptic patients and healthy controls; 3)Obesity as the outcome measure; 4) Availability of comprehensive data; 5) Publication in English. The exclusion criteria were as follows: 1) Exclusion of animal experiments, reviews, and other types of studies; 2) Absence of a healthy control group; 3) Incomplete data; 4) Unextractable or unconvertible data; 5) Low quality, indicated by an Agency for Healthcare Research and Quality(AHRQ) score of 5 or lower,or a Newcastle-Ottawa Scale (NOS) score less than 3. The subjects included in the study included adults and children, and the diagnostic criteria for obesity were used at different ages. In this study, obesity was defined as having a body mass index(BMI) of 25 kg/m2 or higher in adults and being above the 85th percentile of BMI for age in children. We used obesity as an outcome measure for meta-analysis using RevMan, version 5.3. A meta-analysis was conducted on a total of 17 clinical studies, which involved 5329 patients with epilepsy and 480837 healthy controls. These studies were selected from a pool of 1497 articles obtained from four electronic databases mentioned earlier. Duplicate studies were removed based on the search strategies employed. No significant heterogeneity was observed in the outcome measure of obesity in epileptic patients compared with healthy controls(p = 0.01,I2 = 49%). Therefore, a fixed effects model was utilized in this study. The findings revealed a significant difference in obesity prevalence between patients with epilepsy and healthy controls(OR = 1.28, 95%CI: 1.20-1.38, p<0.01). The results of this meta-analysis indicate that epilepsy patients are more prone to obesity than healthy people, so we need to pay attention to the problem of post-epilepsy obesity clinically. Currently, there is a scarcity of largescale prospective studies. Additional clinical investigations are warranted to delve deeper into whether obesity is a comorbidity of epilepsy and whether obesity can potentially trigger epilepsy.

Epilepsy in Patients with Gliomas.

Brain tumor-related epilepsy (BTRE) is a complication that significantly impairs the quality of life and course of treatment of patients with brain tumors. Several recent studies have shed further light on the mechanisms and pathways by which genes and biological molecules in the tumor microenvironment can cause epilepsy. Moreover, epileptic seizures have been found to promote the growth of brain tumors, making the control of epilepsy a critical factor in treating brain tumors. In this study, we summarize the previous research and recent findings concerning BTRE. Expectedly, a deeper understanding of the underlying genetic and molecular mechanisms leads to safer and more effective treatments for suppressing epileptic symptoms and tumor growth.

Clinical characteristics and genetic analysis of pediatric patients with sodium channel gene mutation-related childhood epilepsy: a review of 94 patients.

This study aimed to examine the clinical and gene-mutation characteristics of pediatric patients with sodium channel gene mutation-related childhood epilepsy and to provide a basis for precision treatment and genetic counseling. The clinical data from 94 patients with sodium channel gene mutation-related childhood epilepsy who were treated at Hunan Children's Hospital from August 2012 to December 2022 were retrospectively evaluated, and the clinical characteristics, gene variants, treatment, and follow-up status were analyzed and summarized. Our 94 pediatric patients with sodium channel gene variant-related childhood epilepsy comprised 37 girls and 57 boys. The age of disease onset ranged from 1 day to 3 years. We observed seven different sodium channel gene variants, and 55, 14, 9, 6, 6, 2, and 2 patients had SCNlA, SCN2A, SCN8A, SCN9A, SCN1B, SCN11A, and SCN3A variants, respectively. We noted that 52 were reported variants and 42 were novel variants. Among all gene types, SCN1A, SCN2A, and SCN8A variants were associated with an earlier disease onset age. With the exception of the SCN1B, the other six genes were associated with clustering seizures. Except for variants SCN3A and SCN11A, some patients with other variants had status epilepticus (SE). The main diagnosis of children with SCN1A variants was Dravet syndrome (DS) (72.7%), whereas patients with SCN2A and SCN8A variants were mainly diagnosed with various types of epileptic encephalopathy, accounting for 85.7% (12 of 14) and 88.9% (8 of 9) respectively. A total of five cases of sudden unexpected death in epilepsy (SUDEP) occurred in patients with SCN1A, SCN2A, and SCN8A variants. The proportion of benign epilepsy in patients with SCN9A, SCN11A, and SCN1B variants was relatively high, and the epilepsy control rate was higher than the rate of other variant types. Sodium channel gene variants involve different epileptic syndromes, and the treatment responses also vary. We herein reported 42 novel variants, and we are also the first ever to report two patients with SCN11A variants, thereby increasing the gene spectrum and phenotypic profile of sodium channel dysfunction. We provide a basis for precision treatment and prognostic assessment.

Characteristics and Prognosis of Tumor-Related Epilepsy During Tumor Evolution in Patients With IDH Wild-Type Glioblastoma.

Tumor-related epilepsy is a well-known symptom of glioblastoma. However, the particular characteristics of epileptic seizures related to glioblastoma, isocitrate dehydrogenase (IDH)-wild-type is almost unexplored longitudinally during the whole course of the disease. We assessed tumor-related epilepsy and seizure control during tumor evolution and the prognostic significance of tumor-related epilepsy. We performed an observational, retrospective single-center study at one tertiary referral neuro-oncology surgical center (2000-2020). We included adult patients treated for a newly diagnosed supratentorial glioblastoma, IDH-wild-type with available preoperative and postoperative MRI and with available epileptic seizure status at diagnosis. To determine factors associated with tumor-related epilepsy or seizure control, univariate analyses were performed using the χ2 or Fisher exact tests for categorical variables and the unpaired t test or Mann-Whitney rank-sum test for continuous variables. Predictors associated with tumor-related epilepsy and seizure control in unadjusted analysis were entered into backward stepwise logistic regression models. One thousand six patients were enrolled. The cumulative incidence of tumor-related epilepsy increased during tumor evolution (33.1% at diagnosis, 44.7% after oncologic treatment, 52.4% at progression, and 51.8% at the end-of-life phase) and is related to tumor features (cortex involvement, no necrosis, and small volume). Uncontrolled epileptic seizures increased during tumor evolution (20.1% at diagnosis, 32.0% after oncologic treatment, 46.7% at progression, and 41.1% at the end-of-life phase). Epileptic seizure control after oncologic treatment was related to seizure features (uncontrolled before oncologic treatment and focal-to-bilateral tonic-clonic seizures) and to the extent of resection. Epileptic seizure control at tumor progression was related to seizure features (presence at diagnosis and uncontrolled after oncologic treatment) and to the time to progression. Tumor-related epilepsy at diagnosis was a predictor of a longer overall survival (adjusted hazard ratio, 0.78; 95% CI 0.67-0.90; p < 0.001) independent of age, Karnofsky Performance Status score, tumor location and volume, extent of resection, standard combined chemoradiotherapy, levetiracetam use, and MGMT promoter methylation. The progression of tumor-related epilepsy with the evolution of glioblastoma, IDH-wild-type and the effects of surgery on seizure control argue for proper antiseizure medication and maximal safe resection. Tumor-related epilepsy is an independent predictor of a longer survival.

Minimum spanning tree analysis for epilepsy magnetoencephalography (MEG) data

Aim: Recently, brain network research is actively conducted through the application of graph theory. However, comparison between brain networks is subject to bias issues due to topological characteristics and heterogeneity across subjects. The minimum spanning tree (MST) is a method that is increasingly applied to overcome the thresholding problem. In this study, the aim is to use the MST analysis in comparing epilepsy patients and controls to find the differences between groups. Methods: The MST combines entities for epileptic magnetoencephalography (MEG) data. The MST was applied and compared to 21 left surgery (LT) and 21 right surgery (RT) patients with epilepsy and good postoperative prognosis and a healthy control (HC) group. MST metrics such as betweenness centrality, eccentricity, diameter, and leaf fraction, are computed and compared to describe the integration and efficiency of the network. The MST analysis is applied to each subject, and then the integrated MST is obtained using the distance concept. This approach can be advantageous when comparing the topological structure of patients to controls with the same number of nodes. Results: The HC group showed less topological change and more network efficiency than the epilepsy LT and RT groups. In addition, the posterior cingulate gyrus was found as a hub node only in the patient group in individual and integrated subject data analysis. Conclusions: This study suggests propose that the hippocampus borrows from the default network when one side fails, compensating for the weakened function.

Neighborhood disadvantage and intellectual development in youth with epilepsy

RationaleRecent cross-sectional investigations have demonstrated an adverse impact of socioeconomic disadvantage on cognition and behavior in youth and adults with epilepsy. The goal of this study is to investigate the impact of disadvantage on prospective intellectual development in youth with epilepsy. MethodParticipants were youth, aged 8–18 years, with recent onset epilepsy (n = 182) and healthy first-degree cousin controls (n = 106). The Wechsler Abbreviated Scale of Intelligence (WASI) was administered at baseline and 2 years later. The Neighborhood Atlas identified each family’s Area Deprivation Index via state deciles and national percentiles. WASI data were analyzed by mixed group by time ANOVAs followed by regression analysis to identify other baseline predictors of time 2 outcomes. ResultsYouth with epilepsy demonstrated significant interactions between group and time for both verbal (F = 4.02, df = 1,215, p =.05) and nonverbal (F = 4.57, df = 1,215, p =.04) reasoning, demonstrating that disadvantage was associated with slower cognitive development compared to advantaged youth with epilepsy. Similar interactions were not observed for controls. ConclusionsIn youth with new and recent onset epilepsies, neighborhood-level disadvantage is associated with a negative impact on the development of verbal and nonverbal reasoning skills.

Deep learning distinguishes connectomes from focal epilepsy patients and controls: feasibility and clinical implications.

The application of deep learning models to evaluate connectome data is gaining interest in epilepsy research. Deep learning may be a useful initial tool to partition connectome data into network subsets for further analysis. Few prior works have used deep learning to examine structural connectomes from patients with focal epilepsy. We evaluated whether a deep learning model applied to whole-brain connectomes could classify 28 participants with focal epilepsy from 20 controls and identify nodal importance for each group. Participants with epilepsy were further grouped based on whether they had focal seizures that evolved into bilateral tonic-clonic seizures (17 with, 11 without). The trained neural network classified patients from controls with an accuracy of 72.92%, while the seizure subtype groups achieved a classification accuracy of 67.86%. In the patient subgroups, the nodes and edges deemed important for accurate classification were also clinically relevant, indicating the model's interpretability. The current work expands the evidence for the potential of deep learning to extract relevant markers from clinical datasets. Our findings offer a rationale for further research interrogating structural connectomes to obtain features that can be biomarkers and aid the diagnosis of seizure subtypes.

Integrated Macrogenomics and Metabolomics Explore Alterations and Correlation between Gut Microbiota and Serum Metabolites in Adult Epileptic Patients: A Pilot Study.

Epilepsy (EP) is a complex brain disorder showing a lot of unknows reasons. Recent studies showed that gut microbiota can influence epilepsy via the brain-gut axis. Nevertheless, the mechanism by which gut microbiota affects adult epilepsy still remains unclear. In this study, fecal and serum samples were obtained from patients with epilepsy and normal controls. Using an integrated analysis, sequencing was performed by macrogenomics and high-throughput targeted metabolomics with various bioinformatics approaches. The macrogenomic sequencing revealed significant changes in microbial structure in patients suffering from epilepsy. For example, at the phylum level, the relative abundance of Actinobacteria, Bacteroidetes and Proteobacteria showed an increase in the patients with epilepsy, whereas that of Firmicutes decreased. In addition, the patients with epilepsy had significantly differential metabolite profiles compared to normal controls, and five clusters with 21 metabolites, mainly containing the upregulation of some fatty acids and downregulation of some amino acids. Tryptophan (AUC = 91.81, p < 0.0001), kynurenine (AUC = 79.09, p < 0.01) and 7Z,10Z,13Z,16Z-Docosatetraenoic acid (AUC = 80.95, p < 0.01) may be used as potential diagnostic markers for epilepsy. Differential serum metabolites have effects on tryptophan metabolism, iron death and other pathways. Furthermore, a multiomic joint analysis observed a statistically significant correlation between the differential flora and the differential serum metabolites. In our findings, a macrogenomic analysis revealed the presence of dysregulated intestinal flora species and function in adult epileptic patients. Deeper metabolomic analyses revealed differences in serum metabolites between patients with epilepsy and healthy populations. Meanwhile, the multiomic combination showed connection between the gut microbes and circulating metabolites in the EP patients, which may be potential therapeutic targets.

Effects of attachment styles, childhood traumas, and alexithymia in Turkish patients with epilepsy and functional seizures

IntroductionIn this cross-sectional study, we used self-report scales to compare childhood traumas, attachment styles, and alexithymia among patients with functional seizures (FS) to patients with epilepsy and healthy controls. We also investigated risk factors associated with FS. Material and methodsA total of 44 patients with epilepsy, 14 patients with FS, and 25 healthy controls were included. All participants were over the age of 18 and were referred to the Baskent University Adana Epilepsy and Video-EEG Center. The patients underwent neurological examinations, brain MRIs, and video-EEG evaluations. Epileptic seizures were classified based on video EEG. The control group consisted of healthy individuals without neurological or psychiatric illness and a history of epileptic seizures or syncope. Beck Depression Inventory (BDI), Childhood Trauma Questionnaire (CTQ), Adult Attachment Scale (AAS), and Toronto Alexithymia Scale-20 (TAS-20) were applied to all participants. ResultsPatients with FS had lower educational levels, higher rates of unemployment and single-marital status. The FS group had higher depression, childhood trauma, and alexithymia scores than the other groups. Furthermore, FS patients had a higher prevalence of avoidant attachment. The alexithymia and childhood trauma scores were both correlated with depression. Through the logistic regression analysis, childhood trauma scores and alexithymia were significant risk factors for FS. ConclusionThe use of video-EEG for diagnosing FS can reduce the risk of misdiagnosis and inappropriate antiepileptic treatment. Psychiatric comorbidities, childhood traumas, and alexithymia are prevalent in patients with FS. Therefore, implementing a multidisciplinary treatment approach that addresses the psychological, medical, and social aspects of FS can significantly improve outcomes.