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Background: Anti-seizure medications (ASMs) are the primary therapeutic mode to control seizures in patients with epilepsy. Adherence to the medications is critical to achieving the goals of epilepsy therapy. However, the cost of the medications and the interrupted availability of ASMs contribute to non-adherence to epilepsy treatment. Therefore, this study aimed to assess ASM adherence and its association with self-reported medication availability and affordability. Objective: To assess whether self-reported availability and affordability of Anti-seizure medications affect medication adherence among Epileptic Patients at Eka Kotebe General Hospital, Addis Ababa, Ethiopia, from January 13, 2023 to March 23, 2023. Methods: A hospital-based analytical cross-sectional study was conducted among 357 epileptic patients using the Consecutive sampling method in Eka Kotebe General Hospital, Addis Ababa, Ethiopia. ASM adherence was measured using a self-report 3items questionnaire focusing on medication use patterns of patients from their last visit to the current visit. Statistical packages for Social Sciences 26.0 version statistical software cleaned, coded and analyzed the collected data. Binary logistic regression was fitted, and P-values less than 0.05 were considered to have statistical significance. Result: The prevalence of ASM adherence was 55.2% with 95% CI (50.1%; 60.2%). About two-thirds (61.3%) of patients in this study had limited access to the ASMs or could not afford the medications. Self-reported availability of ASMs (AOR = 2.01, 95% CI = 1.01, 3.98) was significantly associated with ASM adherence. Self-reported affordability of ASMs was associated with ASM adherence in the Bivariate logistic regression analysis; however, when adjusted for other covariates in the multivariable logistic regression, no significant association was observed (p = 0.674). Conclusion and recommendation: Only about half of the epileptic patients adhered to ASMs at Eka Kotebe General Hospital. Self-reported availability of ASMs was an essential factor. Improving access to ASMs is critical to improving adherence and management of epilepsy. [ABSTRACT FROM AUTHOR]

Objective: Approximately 50 million people worldwide have epilepsy and 8–17% of the deaths in patients with epilepsy are attributed to sudden unexpected death in epilepsy (SUDEP). The goal of the present work was to establish a biomarker for SUDEP so that preventive treatment can be instituted. Approach: Seizure activity in patients with SUDEP and non-SUDEP was analyzed, specifically, the scalp EEG extracted muscle activity (SMA) and the average wavelet phase coherence (WPC) during seizures was computed for two frequency ranges (1–12 Hz, 13–30 Hz) to identify differences between the two groups. Main results: Ictal SMA in SUDEP patients showed a statistically higher average WPC value when compared to non-SUDEP patients for both frequency ranges. Area under curve for a cross-validated logistic classifier was 81%. Significance: Average WPC of ictal SMA is a candidate biomarker for early detection of SUDEP. [ABSTRACT FROM AUTHOR]

Objective: 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. Method: 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. Results: 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is a common and serious chronic neurological disorder, and some patients suffer from cognitive dysfunction. We aim to assess the efficacy and safety of acupuncture combined with traditional Chinese herbal for primary epilepsy patients with cognitive impairment. Methods: To search the randomized control trials (RCTs) published before April 20, 2023 from PubMed, Embase, Cochrane Library, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Web of science, and Wanfang Database. The risk of bias within each individual trial was evaluated using the Cochrane Collaboration tool. RevMan5.3 software was used for statistical analysis. The odds ratio (OR) or weighted mean difference (WMD) with a 95% confidence interval (CI) was calculated for each RCT before data pooling. Results: The primary outcomes involve changes in cognitive function and behavioral disturbances. The secondary outcomes focused on quality of life and adverse effects. Conclusion: The results of this review are expected to provide new guidelines for the treatment of primary epilepsy patients with cognitive impairment. Trial registration: This systematic review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) (Registration number: CRD42023415355). [ABSTRACT FROM AUTHOR]

Background: A person with epilepsy experiences recurrent seizures as a result of a persistent underlying disorder. About 50 million people globally are impacted by it, with 4 million of those being in Sub-Saharan Africa. One of the most frequent comorbidities that raise the mortality and morbidity rates of epileptic patients is abnormal Electrocardiographic (ECG) findings. Thus, the purpose of this study is to evaluate the prevalence of abnormal ECG findings in epileptic patients that might lead to increased risk of sudden cardiac death. Methodology: A hospital based cross-sectional study was at Jimma Medical Center of Ethiopia on epileptic patients who were on follow-up at neurologic clinics during the data collection period. The malignant ECG characteristics and was identified using the ECG abnormality tool. To facilitate analysis, the gathered data was imported into Epidata version 3.1 and exported to the SPSS version 26. The factors of abnormal ECG and sudden death risk were examined using bivariate logistic regression. Results: The study comprised 190 epileptic patients, with a mean age of 32 years. There were more men than women, making up 60.2%. A 43.2% (n = 80) frequency of ECG abnormalities was identified. According to the study, early repolarization abnormalities were the most common ECG abnormalities and increased with male sex and the length of time a person had seizures (AOR) of 4.751 and 95% CI (.273,.933), p = 0.029, compared to their female counterparts. Conclusion: The frequency of malignant ECG alterations in epileptic patients on follow-up at Jimma Medical Center in Ethiopia is described in the study. According to the study, there were significant ECG alterations in epileptic individuals. Male gender and longer duration of epilepsy raise the risk of abnormal ECG findings that could result in sudden cardiac death. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy (TLE) is a common form of medically intractable epilepsy. Although seizures originate in mesial temporal structures, there are widespread abnormalities of gray and white matter beyond the temporal lobes that negatively impact functional networks and cognition. Previous studies have focused either on the global impact on functional networks, or on the functional correlates of specific cognitive abilities. Here, we use a two-pronged approach to evaluate the link between whole-brain functional connectivity (FC) anomalies to overall cognitive performance, and how such abnormal connectivity alters the fronto-parietal brain regions involved in working memory (WMem), a cognitive disability often reported by TLE patients. We evaluated 31 TLE patients and 35 healthy subjects through extensive cognitive testing, resting-state functional magnetic resonance imaging (RS-fMRI), and task-based fMRI using Sternberg's task to evaluate WMem. As a group, TLE patients displayed cognitive abnormalities across different domains, although considerable within-group variability was identified. TLE patients showed disruptions of functional networks between and within the default mode network (DMN) and task-positive networks (TPN) resulting in associations with cognitive performance. Furthermore, during the WMem task, TLE patients showed abnormal activity of fronto-parietal regions that were associated with other forms of memory, and alterations of seed-based connectivity analyses. Our results show that different degrees of abnormal functional brain activity and connectivity are related to the severity of disabilities across cognitive spheres. Differential co-activation patterns between patients and healthy subjects suggest potential compensatory mechanisms to preserve adequate cognitive performance. [ABSTRACT FROM AUTHOR]

Background: Although antiseizure medications play a crucial role in the management of epilepsy, their benefit can be compromised due to drug-related problems. Drug therapy problems can lead to poor seizure control, reduced quality of life, and increased morbidity and mortality in patients with epilepsy. However, in our setting, there is limited knowledge about drug therapy problems and the factors that contribute to them. Objective: The aim of this study was to investigate the prevalence and contributing factors of drug-therapy problems among patients with epilepsy. Methodology: A hospital-based prospective observational study was conducted at the neurologic clinic of Ayder Comprehensive Specialized Hospital, located in the Tigray region of Northern Ethiopia. The study included adult patients diagnosed with epilepsy who had been taking at least one antiseizure medication for a minimum of six months. Data were collected by conducting patient interviews and expert reviews of medical and medication records. Prior to data review and interviews, each patient provided written informed consent. Drug therapy problems were identified and classified using Cipolle's method, followed by a consensus review conducted with a panel of experts. Statistical analysis was performed using a statistical software package; SPSS version 22. Binary logistic regression analysis was conducted to determine the contributing factors of drug therapy problems. Statistical significance was determined at p<0.05. Results: A study conducted on 250 participants revealed that 55.2% of the patients experienced one or more drug therapy problems. Our analysis identified a total of 282 drug therapy problems, with a mean of 2±0.52 drug therapy problems per patient. The most commonly observed drug therapy problems were dosage too low (30.0%), noncompliance (22%), adverse drug reaction (18%), and unnecessary drug therapy (16.4%). The commonly involved antiseizure medications in these drug therapy problems were phenytoin (22.8%), Valproic acid (20.8%), and Phenobarbital (18.4%). Furthermore, our findings revealed that combination therapy (AOR: 3.92, 95%CI: 1.19–12.97) and uncontrolled seizure (AOR: 108.37, 95%CI: 38.7–303.6) exhibited significant associations with drug therapy problems. Conclusion: Drug therapy problems were prevalent among patients with epilepsy. The use of combination therapy and the presence of uncontrolled seizures were identified as significant indicators of drug therapy problems. Therefore, more emphasis should be given to patients with multiple medications and uncontrolled seizures. [ABSTRACT FROM AUTHOR]

Background: The world continues to be challenged by the Coronavirus disease 2019 (COVID-19) and preventive measures like maintaining social distancing and lockdowns challenge patients to attend regular follow-ups and get a refill for medication that causes adherence problems. Hence, this study attempts to assess the impact of COVID-19 on treatment follow-up and medication adherence among patients with epilepsy. Method: A total of 276 patients with epilepsy were enrolled in the study. Data collection was carried out through medical record reviews and patient interviews. Patients who visited Zewditu Memorial Hospital from August to September 2021 and those who had follow-up at least for two years before the outbreak of the pandemic were included. The data was analyzed using SPSS v.24. Result: About 69.6% of patients were adherent to their treatment and 83.3% of the patients had a seizure-free period of less than 1 year. Ninety (32.6%) of the participants missed their treatment follow-up during the pandemic, mainly due to fear of being infected with COVID-19. Sixty-eight (24.6%) patients have experienced increased seizure episodes during the pandemic as compared to the previous times. Moreover, 56 (20.3%) participants were not taking their antiseizure medications (ASMs) during the pandemic because of the unavailability of medications and they discontinued hospital visits for their medication refills. Among those who missed their treatment follow-up, 20% had seizure-related physical injuries. Only educational level has a significant association with visiting health facilities during the pandemic. Thus, participants who completed college and above (OR = 2.58, 95% CI (1.32–6.38)) were more likely to attend their follow-up during the pandemics as compared to participants who can't read and write. Conclusion: The present study revealed that COVID-19 might have impacts on treatment follow-up and medication adherence due to fear of infection, travel restrictions and the indirect impact on the availability and affordability of medications. These might lead to poor treatment outcomes like increased seizure frequency and seizure-related physical injuries. [ABSTRACT FROM AUTHOR]

In drug-resistant focal epilepsy, detecting epileptogenic lesions using MRI poses a critical diagnostic challenge. Here, we assessed the utility of MP2RAGE–a T1-weighted sequence with self-bias correcting properties commonly utilized in ultra-high field MRI–for the detection of epileptogenic lesions using a surface-based morphometry pipeline based on FreeSurfer, and compared it to the common approach using T1w MPRAGE, both at 3T. We included data from 32 patients with focal epilepsy (5 MRI-positive, 27 MRI-negative with lobar seizure onset hypotheses) and 94 healthy controls from two epilepsy centres. Surface-based morphological measures and intensities were extracted and evaluated in univariate GLM analyses as well as multivariate unsupervised 'novelty detection' machine learning procedures. The resulting prediction maps were analyzed over a range of possible thresholds using alternative free-response receiver operating characteristic (AFROC) methodology with respect to the concordance with predefined lesion labels or hypotheses on epileptogenic zone location. We found that MP2RAGE performs at least comparable to MPRAGE and that especially analysis of MP2RAGE image intensities may provide additional diagnostic information. Secondly, we demonstrate that unsupervised novelty-detection machine learning approaches may be useful for the detection of epileptogenic lesions (maximum AFROC AUC 0.58) when there is only a limited lesional training set available. Third, we propose a statistical method of assessing lesion localization performance in MRI-negative patients with lobar hypotheses of the epileptogenic zone based on simulation of a random guessing process as null hypothesis. Based on our findings, it appears worthwhile to study similar surface-based morphometry approaches in ultra-high field MRI (≥ 7 T). [ABSTRACT FROM AUTHOR]

Introduction: Epilepsy has been found to affect caregivers' quality of life, lifestyle, psychological health, social well-being, and working time. Caregivers in Uganda as in the rest of the world are important in assisting a person with epilepsy in complying with medical directions and are actively involved in communicating with healthcare professionals. Little is known about the lived experiences of caregivers of persons afflicted with epilepsy in Uganda. The purpose of this study was to determine the lived experiences of caregivers of persons with epilepsy attending the epilepsy clinic at Mbale regional referral hospital, eastern Uganda. Methods and materials: The caregivers' lived experiences were elicited directly from them and their health workers who work with them in the care of the patients. Forty participants which consisted of 30 caregivers and 10 key informant health workers were selected for the study through purposive sampling. Face-to-face in-depth interviews with an unstructured interview guide were conducted to gather participants' information. The principal investigator conceptualized the interview guide, the guide was then reviewed by co-investigators, and revised and approved as the final data collection instrument after an extensive and comprehensive literature review. The interview guide comprised two sections; the first section comprised the questions that elicited the participants' social-demographic information. The second section comprised questions that explored caregivers' experiences of persons afflicted with epilepsy. Notations were taken and a digital recorder was used purposely for audio recordings. All interviews lasted for an hour and were audio-recorded with the participant's consent. An inductive thematic analysis was employed and adopted to identify the patterns emerging from the texts. Results: The caregivers majorly perceived epilepsy as a burden. Four main themes were revealed from the analysis and these are: psychological burdens which included, worries about the future of the patient, being looked down upon; social burdens which entailed, affected public relations, feelings of stigma; an economic burden which included interference with the source of income, affected productivity at work; and physical burdens which included, Feelings of uneasiness and disrupted sleep among others. Conclusion: The caregivers majorly perceived epilepsy as a serious burden. This burden can be psychological, social, economic, and physical. Therefore, services and plans targeting patients with epilepsy need to consider the burden that caregivers encounter to comprehensively manage epilepsy. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is a prevalent disease that requires personalized care to control seizures, reduce side effects, and ameliorate the burden of comorbidities. Smoking is a major cause of preventable death and disease. There is evidence that patients with epilepsy smoke at high rates and that smoking may increase seizure frequency. However, there is a lack systematically synthesized evidence on the interactions between epilepsy and seizures and smoking, tobacco use, vaping, and smoking cessation. Methods and analysis: This scoping review protocol guided by the Joanna Briggs Institute Manual for Evidence Synthesis and the PRISMA Extension for Scoping Reviews will investigate what is known about the interactions between smoking and epilepsy. This review will include the population of persons with all types of epilepsy or seizures and examine an inclusive list of concepts including tobacco use, vaping, nicotine replacement, and smoking cessation. The MEDLINE, Embase, APA Psycinfo, CINAHL, Cochrane, Scopus, and Web of Science databases will be searched. Following systematic screening of records, data will be charted, synthesized, and summarized for presentation and publication. Ethics and dissemination: No ethical approval is required for this literature-based study. The results of this scoping review will be submitted for publication in a peer-reviewed journal. This synthesis will be informative to clinicians and direct further research that may improve health outcomes for people with epilepsy. Registration: This protocol is registered with the Open Science Framework (DOI: https://doi.org/10.17605/OSF.IO/D3ZK8). [ABSTRACT FROM AUTHOR]

Epilepsy is a common, serious condition. Fortunately, seizure risk decreases with increasing seizure-free time on antiseizure medications (ASMs). Eventually, patients may consider whether to stop ASMs, which requires weighing treatment benefit versus burden. We developed a questionnaire to quantify patient preferences relevant to ASM decision-making. Respondents rated how concerning they would finding relevant items (e.g., seizure risks, side effects, cost) on a Visual Analogue Scale (VAS, 0–100) and then repeatedly chose the most and least concerning item from subsets (best-worst scaling, BWS). We pretested with neurologists, then recruited adults with epilepsy who were seizure-free at least one year. Primary outcomes were recruitment rate, and qualitative and Likert-based feedback. Secondary outcomes included VAS ratings and best-minus-worst scores. Thirty-one of 60 (52%) contacted patients completed the study. Most patients felt VAS questions were clear (28; 90%), easy to use (27; 87%), and assessed preferences well (25; 83%). Corresponding results for BWS questions were 27 (87%), 29 (97%), and 23 (77%). Physicians suggested adding a 'warmup' question showing a completed example and simplifying terminology. Patients suggested ways to clarify instructions. Cost, inconvenience of taking medication, and laboratory monitoring were the least concerning items. Cognitive side effects and a 50% seizure risk in the next year were the most concerning items. Twelve (39%) of patients made at least one 'inconsistent choice' for example ranking a higher seizure risk as lower concern compared with a lower seizure risk, though 'inconsistent choices' represented only 3% of all question blocks. Our recruitment rate was favorable, most patients agreed the survey was clear, and we describe areas for improvement. 'Inconsistent' responses may lead us to collapse seizure probability items into a single 'seizure' category. Evidence regarding how patients weigh benefits and harms may inform care and guideline development. [ABSTRACT FROM AUTHOR]

Mitochondrial sirtuins have diverse role specifically in aging, metabolism and cancer. In cancer, these sirtuins play dichotomous role as tumor suppressor and promoter. Previous studies have reported the involvement of sirtuins in different cancers. However, till now no study has been published with respect to mitochondrial sirtuins and glioma risks. Present study was purposed to figure out the expression level of mitochondrial sirtuins (SIRT3, SIRT4, SIRT5) and related genes (GDH, OGG1-2α, SOD1, SOD2, HIF1α and PARP1) in 153 glioma tissue samples and 200 brain tissue samples from epilepsy patients (taken as controls). To understand the role of selected situins in gliomagenesis, DNA damage was measured using the comet assay and oncometabolic role (oxidative stress level, ATP level and NAD level) was measured using the ELISA and quantitative PCR. Results analysis showed significant down-regulation of SIRT4 (p = 0.0337), SIRT5 (p<0.0001), GDH (p = 0.0305), OGG1-2α (p = 0.0001), SOD1 (p<0.0001) and SOD2 (p<0.0001) in glioma patients compared to controls. In case of SIRT3 (p = 0.0322), HIF1α (p = 0.0385) and PARP1 (p = 0.0203), significant up-regulation was observed. ROC curve analysis and cox regression analysis showed the good diagnostic and prognostic value of mitochondrial sirtuins in glioma patients. Oncometabolic rate assessment analysis showed significant increased ATP level (p<0.0001), NAD+ level [(NMNAT1 (p<0.0001), NMNAT3 (p<0.0001) and NAMPT (p<0.04)] and glutathione level (p<0.0001) in glioma patients compared to controls. Significant increased level of damage ((p<0.04) and decrease level of antioxidant enzymes include superoxide dismutase (SOD, p<0.0001), catalase (CAT, p<0.0001) and glutathione peroxidase (GPx, p<0.0001) was observed in patients compared to controls. Present study data suggest that variation in expression pattern of mitochondrial sirtuins and increased metabolic rate may have diagnostic and prognostic significance in glioma patients. [ABSTRACT FROM AUTHOR]

This study sought to identify differences in cannabis use and perceptions about cannabis in mitigating seizure-related symptoms in patients with epilepsy, and to evaluate differences in these patterns between drug-resistant versus pharmacoresponsive epilepsy. A collection of self-report surveys completed by patients with epilepsy (n = 76) were used to retrospectively compare differences in those with drug-resistant versus pharmacoresponsive epilepsy regarding 1) proportion who used cannabis, 2) frequency of use, 3) method of use, and 4) reason for use. A Cochran-Armitage test for trend indicated that of patients who used cannabis, a higher proportion of patients in the drug-resistant group used more frequently than in the pharmacoresponsive group. Almost half (48%) of those in the drug-resistant group reported daily use compared to approximately a third (36%) of those in the pharmacoresponsive group. Additionally, no patient in either group reported that cannabis was harmful in relation to seizure-related symptoms. Results from this study highlight the need for epilepsy providers to formally assess patients' perceptions and use of non-prescribed cannabis to inform clinical care decisions, particularly in the drug-resistant epilepsy population. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is the most common neurological disorder, which is characterized by persistent derangement of the nervous system due to an abrupt excessive discharge of the group of neurons from the cerebrum. For developing young people with epilepsy coping with the challenges of living with epilepsy and adjusting normative tasks associated with adolescence is stressful in all domains of the lives of young people with epilepsy. But in Ethiopia, published literature regarding the lived experience of young people with epilepsy is lacking. Objectives: This study aims to explore lived experience of young people with epilepsy. Methods: A qualitative interview study was conducted in Bahir Dar city government specialized and referral Hospitals, from February to April, 2021. Using the rule of saturation, a total of 11 study participants (age 12–24) were selected using hetrogenious types of purposive sampling technique. The data were collected through semi structured interviews technique with the aid of audio recorder. Semi-structured interview guide and observation checklist for care context in health facilities were used. The collected data was transcribed word by word and translated conceptually. The Data were analyzed using thematic approach. The credibility, dependability, Conformability and transferability of the study were assured using different techniques such as peer debriefing, member checking; audit Trail, thick description and purposeful sampling. Atlas- ti version7 software was used to facilitate data analysis. Results: The participants' narratives revealed two main themes: 'experiences due epilepsy' and 'coping strategies to wards epilepsy'. Experience due to epilepsy' was described by young people with epilepsy in terms of psychosocial, physical, economical and health care related experiences. They described coping strategies towards epilepsy in terms of finding support from family and society as well as religious institutions and other traditions as copping strategy. Conclusion: Even though young people with epilepsy had suffered a lot of hurtful experiences, they reported coping strategies towards epilepsy that include support from various sources. These types of findings have implications for social work interventions for young people living with epilepsy. [ABSTRACT FROM AUTHOR]

Introduction: Metabolic syndrome is a group of metabolic risk factors which are associated with an increased risk of cardiovascular disease and type2 diabetes. Nowadays, several studies have shown that the burden of metabolic syndrome is increasing among epileptic patients, and leads to MS-associated complications, including cardiovascular disease. However, getting published documents has been limited in Ethiopia and the study area. Therefore, we aimed to analyze the magnitude and associated factors of metabolic syndrome among epileptic patients in Dessie Comprehensive Specialized Hospital in compression with respective controls. Methods: Hospital-based comparative cross-sectional study design was implemented from June 25 to August 20, 2021. A total of 204 participants with an equal number of cases and controls (n = 102 each) were included. The data was collected through face-to-face interviews and biochemical analyses such as fasting blood glucose and lipid profiles were done through the enzymatic technique. The magnitude of metabolic syndrome was determined using both National Cholesterol Education Program Adult Treatment Panel III and International Diabetes Federation definition criteria. The STATA version 14 was used for statistical data analysis, and a comparison of categorical and continuous variables was done with χ2 and an independent t-test, respectively. The multivariable binary logistic regression analysis was used to identify factors associated with metabolic syndrome, and variables having a P-value of <0.05 were considered statistically significant. Result: The prevalence of metabolic syndrome among the epileptic group was (25.5% in National Cholesterol Education Program Adult Treatment Panel III and 23.5% in International Diabetes Federation criteria), whereas it was 13.7% in National Cholesterol Education Program Adult Treatment Panel III and 14.7% in International Diabetes Federation criteria among control groups. According to the International Diabetes Federation criteria, low physical activity (adjusted odds ratio = 4.73, 95% CI: 1.08–20.68), taking multiple antiepileptic drugs (adjusted odds ratio = 8.08, 95% CI: 1.52–42.74), having a total cholesterol level of ≥ 200 mg/dl (adjusted odds ratio = 5.81, 95%: 1.32–41.13) and body mass index (adjusted odds ratio = 1.57, 95% CI = 1.16–2.11) were significantly associated with metabolic syndrome among epileptic participants. Applying National Cholesterol Education Program Adult Treatment Panel III criteria, taking multiple antiepileptic drugs (adjusted odds ratio = 6.81, 95% CI: 1.29–35.92), having a total cholesterol level > 200 mg/dl (adjusted odds ratio = 7.37, 95% CI: 1.32–41.13) and body mass index (adjusted odds ratio = 1.53, 96% CI: 1.16–2.01) were also significantly associated. Conclusion: The prevalence of metabolic syndrome among epileptic patients was higher than that of control groups and reaches statistically significant by National Cholesterol Education Program Adult Treatment Panel III. Being on multiple antiepileptic drugs, body mass index, having low physical activity and raised total cholesterol were significantly associated with metabolic syndrome among the epileptic group. Therefore, it is better to focus on controlling weight, having sufficient physical exercise, and regular monitoring of total cholesterol levels in epileptic patients. [ABSTRACT FROM AUTHOR]

Objective: This study offers meta-analytic data on the potential association between epilepsy and depression especially for the prevalence of depression in epilepsy or vice versa. Methods: The relevant studies were searched and identified from nine electronic databases. Studies that mentioned the prevalence and/or incidence of epilepsy and depression were included. Hand searches were also included. The search language was English and the search time was through May 2022. Where feasible, random-effects models were used to generate pooled estimates. Results: After screening electronic databases and other resources, 48 studies from 6,234 citations were included in this meta-analysis. The period prevalence of epilepsy ranged from 1% to 6% in patients with depression. In population-based settings, the pooled period prevalence of depression in patients with epilepsy was 27% (95% CI, 23–31) and 34% in clinical settings (95% CI, 30–39). Twenty studies reported that seizure frequency, low income, unemployment of the patients, perception of stigma, anxiety, being female, unmarried status, disease course, worse quality of life, higher disability scores, and focal-impaired awareness seizures were risk factors for depression. Conclusion: Our study found that epilepsy was associated with an increased risk of depression. Depression was associated with the severity of epilepsy. [ABSTRACT FROM AUTHOR]

The reliable identification of the irritative zone (IZ) is a prerequisite for the correct clinical evaluation of medically refractory patients affected by epilepsy. Given the complexity of MEG data, visual analysis of epileptiform neurophysiological activity is highly time consuming and might leave clinically relevant information undetected. We recorded and analyzed the interictal activity from seven patients affected by epilepsy (Vectorview Neuromag), who successfully underwent epilepsy surgery (Engel > = II). We visually marked and localized characteristic epileptiform activity (VIS). We implemented a two-stage pipeline for the detection of interictal spikes and the delineation of the IZ. First, we detected candidate events from peaky ICA components, and then clustered events around spatio-temporal patterns identified by convolutional sparse coding. We used the average of clustered events to create IZ maps computed at the amplitude peak (PEAK), and at the 50% of the peak ascending slope (SLOPE). We validated our approach by computing the distance of the estimated IZ (VIS, SLOPE and PEAK) from the border of the surgically resected area (RA). We identified 25 spatiotemporal patterns mimicking the underlying interictal activity (3.6 clusters/patient). Each cluster was populated on average by 22.1 [15.0–31.0] spikes. The predicted IZ maps had an average distance from the resection margin of 8.4 ± 9.3 mm for visual analysis, 12.0 ± 16.5 mm for SLOPE and 22.7 ±. 16.4 mm for PEAK. The consideration of the source spread at the ascending slope provided an IZ closer to RA and resembled the analysis of an expert observer. We validated here the performance of a data-driven approach for the automated detection of interictal spikes and delineation of the IZ. This computational framework provides the basis for reproducible and bias-free analysis of MEG recordings in epilepsy. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is one of the most important causes of acquired structural epilepsy, post-traumatic epilepsy (PTE), however, efficient preventative measures and treatment are still not available to patients. Preclinical studies indicated biperiden, an anticholinergic drug, as a potential drug to modify the epileptogenic process. The main objective of this clinical trial is to evaluate the efficacy of biperiden as an antiepileptogenic agent in patients that suffered TBI. Methods: This prospective multicenter (n = 10) interventional study will include 312 adult patients admitted to emergency care units with a diagnosis of moderate or severe TBI. Following inclusion and exclusion criteria, patients will be randomized, using block randomization, to receive double-blind treatment with placebo or biperiden for 10 days. Follow-up will occur at specific time windows up to 2 years. Main outcomes are incidence of PTE after TBI and occurrence of severe adverse events. Other outcomes include exploratory investigation of factors that might have benefits for the treatment or might influence its results, such as genetic background, clinical progression, electroencephalographic abnormalities, health-related quality of life and neuropsychological status. Analyses will be conducted following the safety, intention-to-treat and efficacy concepts. Discussion: We hypothesize that biperiden treatment will be effective to prevent or mitigate the development of post-traumatic epilepsy in TBI patients. Other health measures from this population also may benefit from treatment with biperiden. Trial registration: ClinicalTrials.gov, NCT04945213. Registered on June 30, 2021. [ABSTRACT FROM AUTHOR]

Background: Despite the high prevalence of epilepsy and multiple barriers to care in people with intellectual disability, the risk of returning to hospital after an admission for epilepsy is largely unknown. In this study, we sought to quantify and compare readmission and emergency department (ED) presentations after hospitalisation for epilepsy in people with and without intellectual disability. Methods and findings: Using linked administrative datasets, we conducted a retrospective cohort study of people aged 5–64 years with an acute hospitalisation for epilepsy from 2005–2014 in New South Wales, Australia. Acute readmission and ED presentation rates within 30, 90, and 365 days of the index hospitalisation were estimated and compared between people with and without intellectual disability using modified Poisson regression. Of 13537 individuals with an index hospitalisation, 712 children and 1862 adults had intellectual disability. Readmission and ED presentation after the index hospitalisation were common in people with intellectual disability. Within 30 days, 11% of children and 15.6% of adults had an all-cause readmission and 18% of children and 23.5% of adults had an ED presentation. Over 60% of both children and adults presented to an ED within a year. Neurological, respiratory, and infectious conditions were overrepresented reasons for readmission in people with intellectual disability. Age-adjusted relative risks (RRs) within each period showed a higher risk of readmission and ED presentation in children and adults with intellectual disability than without. Most RRs remained statistically significant after controlling for covariates. The largest adjusted RRs were observed for readmission for epilepsy (RR 1.70, 95% CI: 1.42 to 2.04) and non-epilepsy related conditions (RR 1.73, 95%: CI 1.43 to 2.10) in children. Study limitations include lack of clinical data. Conclusions: Increased risk of returning to acute care after epilepsy hospitalisation suggests there is a need to improve epilepsy care for people with intellectual disability. We recommend research into strategies to improve management of both seizures and comorbidity. [ABSTRACT FROM AUTHOR]

Background: The care of epileptic patients is complicated by the cognitive adverse effect of the drug, disease, pharmacokinetics, and pharmacodynamics properties of antiepileptic drugs which in turn intensify the risk of drug therapy problems among epileptic patients. Objective: To assess drug therapy problems and predicting factors among ambulatory epileptic patients at Jimma University Medical Center, Southwest Ethiopia, from September 2020 to May 2021. Methodology: A hospital-based prospective observational study was conducted. A semi-structured questionnaire was used to collect data from patients as well as from charts. Drug therapy problems were identified using Cipolle's, Morley, and Strand drug therapy problem identification and classification method. Data were entered into Epi data manager version 4.6 and exported to statistical software package for social science version 23.0 for analysis. Multiplestepwise backward logistic regression analysis was carried out to identify predictors of drug therapy problems. The 95% CI was used to show an association between the dependent and independent variables. P-value < 0.05 was considered as statistically significant. Results: Of the total 320 epileptic patients 224(70.0%) patients had at least one drug therapy problem. A total of 395 drug therapy problems were identified among two hundred twenty-four patients with an average of 1.2 drug therapy problems per patient. The frequently identified drug therapy problems were non-compliance 115(29.11), adverse drug reaction 110(27.84%), and dose too low 103(26%). Getting of a drug by purchasing [AOR = 4.6,95%CI:(2.05–10.7)], poorly involvement of the patients in therapeutic decision making [AOR = 3.02,95%CI:(1.5–6.06)], the number of medications ≥ two [AOR = 5.3,95%CI:(1.2–22.9)] and having had uncontrolled seizure [AOR = 10.9,95%CI:(4.9–24.2)] were independent predictors of drug therapy problems. Conclusions: Drug therapy problems were common among epileptic patients in the study area. Patients who were getting their drugs by purchasing, poorly involved in therapeutic decision making, having had an uncontrolled seizure, and taking two and above drugs were more likely to experience drug therapy problems. Therefore, due attention should be given to patients with the aforementioned problems to decrease the occurrence of drug therapy problems and improve overall outcomes among epileptic patients. [ABSTRACT FROM AUTHOR]

We propose a novel neural network architecture, SZTrack, to detect and track the spatio-temporal propagation of seizure activity in multichannel EEG. SZTrack combines a convolutional neural network encoder operating on individual EEG channels with recurrent neural networks to capture the evolution of seizure activity. Our unique training strategy aggregates individual electrode level predictions for patient-level seizure detection and localization. We evaluate SZTrack on a clinical EEG dataset of 201 seizure recordings from 34 epilepsy patients acquired at the Johns Hopkins Hospital. Our network achieves similar seizure detection performance to state-of-the-art methods and provides valuable localization information that has not previously been demonstrated in the literature. We also show the cross-site generalization capabilities of SZTrack on a dataset of 53 seizure recordings from 14 epilepsy patients acquired at the University of Wisconsin Madison. SZTrack is able to determine the lobe and hemisphere of origin in nearly all of these new patients without retraining the network. To our knowledge, SZTrack is the first end-to-end seizure tracking network using scalp EEG. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is a chronic non-communicable brain disorder and the second most burdensome disease in terms of disability-adjusted life years which is characterized by recurrent epileptic seizures, and a constant threat to the quality of life of the patient. Nearly 80% of people with epilepsy live in low- and middle-income countries and the risk of premature death in people with epilepsy is up to three times higher than for the general population. In many parts of the world, people with epilepsy and their families suffer from stigma and discrimination. This study was aimed to assess the quality of life and associated factors among adult people living with epilepsy using the world health organization quality of life assessment tool. Methods: Institution-based cross-sectional study design was conducted on 419 epileptic patients using a systematic random sampling technique. The data were collected using the WHOQOL-BREF questionnaire. The data were entered into EpiData version 3.1 and exported to SPSS version 25 software for further analysis and bivariate and multivariable binary logistic regression analyses were done to identify factors associated with the dependent variable. The level of significance was declared as P value <0.05. Result: A total of 402 epileptic patients with a median age of 28 years were involved in the study. The result of this study was revealed that 47.8% (95% CI: 42%, 52%) of the respondents had poor quality of life. Respondents who were in the middle age group (AOR = 0.36, 95% CI: 0.19, 0.70), lower educational level (AOR = 3.11, 95%CI: 1.35, 7.15), those who had low drug adherence (AOR = 8.36, 95%CI: (2.41, 28.98) comorbid anxiety, (AOR = 3.63, 95% CI: 2.55, 8.42) and depression (AOR = 3.85, 95% CI: 2.16, 6.82) were found to be significantly associated with poor quality of life of epilepsy patients. Conclusion: This study revealed that almost one in two epileptic patients had poor quality of life. Age of the respondents, lower educational level, comorbid anxiety and depression, and lower adherence to drugs were significantly associated with poor quality of life. Therefore, health institutions and clinicians should not focus only on the treatment of the disease itself rather they should address diseases' impact on the quality of life of patients. [ABSTRACT FROM AUTHOR]

To quickly and efficiently recognize abnormal patterns from large-scale time series and pathological signals in epilepsy, this paper presents here a preliminary RSW&TST framework for Multiple Change-Points (MCPs) detection based on the Random Slide Window (RSW) and Trigeminal Search Tree (TST) methods. To avoid the remaining local optima, the proposed framework applies a random strategy for selecting the size of each slide window from a predefined collection, in terms of data feature and experimental knowledge. For each data segment to be diagnosed in a current slide window, an optimal path towards a potential change point is detected by TST methods from the top root to leaf nodes with O(log3(N)). Then, the resulting MCPs vector is assembled by means of TST-based single CP detection on data segments within each of the slide windows. In our experiments, the RSW&TST framework was tested by using large-scale synthetic time series, and then its performance was evaluated by comparing it with existing binary search tree (BST), Kolmogorov-Smirnov (KS)-statistics, and T-test under the fixed slide window (FSW) approach, as well as the integrated method of wild binary segmentation and CUSUM test (WBS&CUSUM). The simulation results indicate that our RSW&TST is both more efficient and effective, with a higher hit rate, shorter computing time, and lower missed, error and redundancy rates. When the proposed RSW&TST framework is executed for MCPs detection on pathological ECG (electrocardiogram)/EEG (electroencephalogram) recordings of people in epileptic states, the abnormal patterns are roughly recognized in terms of the number and position of the resultant MCPs. Furthermore, the severity of epilepsy is roughly analyzed based on the strength and period of signal fluctuations among multiple change points in the stage of a sudden epileptic attack. The purpose of our RSW&TST framework is to provide an encouraging platform for abnormal pattern recognition through MCPs detection on large-scale time series quickly and efficiently. [ABSTRACT FROM AUTHOR]

Background: Globally, epilepsy is the commonest neurological disorder in adults. It has significant health and economic consequences to the affected individuals and the family. There is ample evidence that epileptic patients are at increased risk of poor sleep quality than the general population. However, there is limited evidence on sleep quality among epileptic patients and associated factors in Ethiopia. Therefore, this study investigated the prevalence of poor sleep quality and associated factors among adult patients with epilepsy. Method: Institutional based cross-sectional study was conducted among adult epileptic patients attending follow-up care at referral hospitals in the Amhara region. A total of 575 epileptic patients were recruited using a stratified systematic random sampling technique. An interviewer-administered semi-structured questionnaire and record review were used for data collection. To assess sleep quality the pretested Pittsburgh Sleep Quality Index (PSQI) tool was used. A binary logistic regression model was used to assess factors associated with poor sleep quality. Variables with a p-value less than 0.2 in the bivariable binary logistic regression analysis were considered for the multivariable binary logistic regression analysis. In the multivariable binary logistic regression analysis, the Adjusted Odds Ratio (AOR) with the 95% Confidence Interval (CI) were reported to declare the statistical significance and strength of association. Model fitness was assessed using the Hosmer-Lemeshow test and was adequate (p>0.05). Multicollinearity of the independent variables was assessed using the Variance Inflation Factor (VIF) and the mean VIF was less than 10. Results: A total of 565 participants were enrolled in the study with a response rate of 98.3%. The prevalence of poor sleep quality among adult epileptic patients was 68.8% [95% CI: 64.8%, 72.5%]. In the multivariable binary logistic regression, being unable to read and write [AOR = 3.16, 95%CI: 1.53, 6.51], taking polytherapy treatment [AOR = 2.10, 95% CI: 1.37, 3.21], poor medication adherence [AOR = 2.53, 95%CI: 1.02, 6.23] and having poor support [AOR = 2.72, 95%CI: 1.53, 4.82] and moderate social support [AOR = 1.89, 95%CI: 1.05, 3.41] were significantly associated with higher odds of poor sleep quality. Conclusion and recommendation: Poor sleep quality is a major public health concern in Ethiopia. The patient's level of education, number of medication use, medication adherence, and social support were found significant predictors of poor sleep quality. These findings highlight improving medication adherence and social support are effective strategies to improve the sleep quality of epileptic patients. Besides, it is better to give special emphasis to those epileptic patients with a low level of education and taking polytherapy to enhance sleep quality. [ABSTRACT FROM AUTHOR]

Background: Childhood epilepsy is a major public health problem worldwide. Even though anti-seizure medications (ASM) have been demonstrated to control seizures, children with epilepsy continue to have frequent seizures. There is a scarcity of data on seizure control status among pediatric epileptic patients in Ethiopia. The aim of this study was to assess seizure control status and associated factors among pediatric epileptic patients. Methods: A hospital based cross-sectional study was done on 261 pediatric epileptic patients being followed up at the University of Gondar Comprehensive and Specialized Hospital, Northwest Ethiopia, from May 11 to August 11, 2019. The data were collected through caregiver interviews and patients' medical records. All independent variables with p value of ≤ 0.2 in univariate analysis were taken to multivariable analysis. Adjusted odds ratio (AOR) with a 95% confidence interval was computed to see the predictors of seizure control status. Level of statistical significance was declared if p-value < 0.05. Result: From a total of 261 patients, 159 (60.9%) were males and had a mean age was 10.16 ± 4.62 years. More than half (57.1%) of participants were urban dwellers. Almost all (98.5%) were diagnosed with generalized tonic-clonic seizures. Majority (75.1%) of the patients were on mono-therapy. Forty-six (17.6%) of the patients reported adverse effects related to ASMs. Two hundred-three (77.8%) of the patients were adherent to their medications. Nearly half (49.0%) of the patients had controlled seizures. Urban residency (AOR: 2.12; 95% CI: 1.15–3.89; P = 0.016), adherence to medication (AOR: 3.92; 95% CI: 1.84–8.36; P < 0.001), use of combined ASM(AOR: 0.29; 95% CI: 0.14–0.59; P = 0. 001), durations of ASM use [2–5 years (AOR: 5.81; 95% CI: 2.89–11.70; P <0.001) and >5years (AOR: 4.80; 95% CI: 1.91–12.09; P = 0.001)]were significantly associated with seizure control status. Conclusion: Inadequate numbers of pediatric epileptic patients' at the Ethiopian neurologic clinic achieved seizure control. Coming from a rural area, non-adherence to ASMs, use of multiple ASMs, and the use of ASMs for <2years were found to have a significant association with poorer seizure control, needing special attention to get control of seizure. Caregivers should closely monitor and address any barriers that contribute to ASM non-adherence and adverse drug events. [ABSTRACT FROM AUTHOR]

Introduction: Depression is a commonly overwhelming problem among patients with epilepsy which compromises their quality of life especially in developing countries. Previously limited studies were conducted using Becks Depression Inventory tool in Ethiopia. The aim of this study's objective was to determine the prevalence of depression and associated factors among patients with epilepsy. Methods: Institution based cross-sectional study was employed at the University of Gondar Comprehensive Specialized Hospital from March 01–30, 2019.A total of 370 participants were selected using an interview administered structured questionnaire. Hospital Anxiety and Depression Scale was used to assess the prevalence of depression.Multivariable logistic regression analysis was done to investigate potential predictors and variables with a P-value of < 0.05 and a 95% confidence interval were considered statistically significant. Results: A total of 370 study participants participated with a response rate of 92%. From the total respondents 37% experienced depression. Perceived stigma (AOR = 3.89, CI: 2.27, 6.68), educational status (AOR = 0.48, CI: 0.25, 0.92), residence (AOR = 0.5, CI: 0.28, 0.89), frequency of seizure (AOR = 2.07, CI: 1.01, 4.23) and social support (AOR = 2.73, CI: 1.41–5.31) were significantly associated with depression status. Conclusion: This study revealed that prevalence of depression among Epileptic patients was high. Perceived stigma, educational status, residence, frequency of seizure and social support were significantly associated with depression status. Thus, health care workers better to give more emphasis to patients with perceived stigma, higher number of seizure frequency and to those with poor level of social support. [ABSTRACT FROM AUTHOR]

Objective: To assess the magnitude and factors associated with depression and anxiety among people with epilepsy and attending out-patient treatment at central Gondar zone primary public hospitals, northwest, Ethiopia. Method: An institutional based cross-sectional study was conducted from May—June, 2020 at central Gondar zone primary public hospitals. A total of 589 participants were chosen by systematic sampling technique. Data was collected by utilizing Amharic version interviewer-administered structured and semi-structured questioners. Depression and anxiety were assessed by using hospital anxiety and depression scale. Bivariate and multivariate logistic regression analysis was done to recognize variables related to both depression and anxiety. Association was described by using "adjusted odds ratio" (AOR) along with 95% full Confidence interval (CI). Finally, P-values < 0.05 in adjusted analysis were taken as a cut off for significant association. Result: Out of 556 participants included in the study, 30.9%, 33.1% had depression and anxiety respectively. Being divorced/widowed (AOR = 2.43, 95% CI, 1.18–4.99), using two and above number of antiepileptic medications (AOR = 1.77,95% CI,1.02–3.09), very frequent seizure frequency (AOR = 2.68, 95% CI,1.30–5.51), current substance use (AOR = 1.82, 95% CI, 1.03–3.22), perceived stigma (AOR = 5.67,95% CI,3.14–8.18), and hazardous alcohol use (AOR = 2.84, 95% CI,1.32–6.09) were statistically associated with depression. While, being a single (AOR = 1.65, 95% CI, 1.04–2.63), using two and above number of antiepileptic medications (AOR = 2.27, 95% CI, 1.42–3.62), duration of illness ≥16 years (AOR = 2.82, 95% CI, 1.26–6.31), and perceived stigma (AOR = 2.49, 95% CI, 1.63–3.82) were statistically associated with anxiety at a p-value < 0.05. Conclusion: This study showed that the magnitude of depression and anxiety were relatively high among people with epilepsy. Using two and above number of antiepileptic medications and perceived stigma were statistically associated with both depression and anxiety. Screening, early identification and providing appropriate intervention of depression and anxiety among people with epilepsy should be great concern for the health care providers. [ABSTRACT FROM AUTHOR]

The genetic influence in epilepsy, characterized by unprovoked and recurrent seizures, is through variants in genes critical to brain development and function. We have carried out variant calling in Mesial Temporal Lobe Epilepsy (MTLE) patients by mapping the RNA-Seq data available at SRA, NCBI, USA onto human genome assembly hg-19. We have identified 1,75,641 SNVs in patient samples. These SNVs are distributed over 14700 genes of which 655 are already known to be associated with epilepsy. Large number of variants occur in the 3'-UTR, which is one of the regions involved in the regulation of protein translation through binding of miRNAs and RNA-binding proteins (RBP). We have focused on studying the structure-function relationship of the 3'-UTR SNVs that are common to at-least 10 of the 35 patient samples. For the first time we find SNVs exclusively in the 3'-UTR of FGF12, FAR1, NAPB, SLC1A3, SLC12A6, GRIN2A, CACNB4 and FBXO28 genes. Structural modelling reveals that the variant 3'-UTR segments possess altered secondary and tertiary structures which could affect mRNA stability and binding of RBPs to form proper ribonucleoprotein (RNP) complexes. Secondly, these SNVs have either created or destroyed miRNA-binding sites, and molecular modeling reveals that, where binding sites are created, the additional miRNAs bind strongly to 3'-UTR of only variant mRNAs. These two factors affect protein production thereby creating an imbalance in the amounts of select proteins in the cell. We suggest that in the absence of missense and nonsense variants, protein-activity imbalances associated with MTLE patients can be caused through 3'-UTR variants in relevant genes by the mechanisms mentioned above. 3'-UTR SNV has already been identified as causative variant in the neurological disorder, Tourette syndrome. Inhibition of these miRNA-mRNA bindings could be a novel way of treating drug-resistant MTLE patients. We also suggest that joint occurrence of these SNVs could serve as markers for MTLE. We find, in the present study, SNV-mediated destruction of miRNA binding site in the 3'-UTR of the gene encoding glutamate receptor subunit, and, interestingly, overexpression of one of this receptor subunit is also associated with Febrile Seizures. [ABSTRACT FROM AUTHOR]

Objective: Focal cortical dysplasia (FCD) represents a heterogeneous group of disorders of the cortical formation and is one of the most common causes of epilepsy. Magnetic resonance imaging (MRI) is the modality of choice for detecting structural lesions, and the surgical prognosis in patients with MR lesions is favorable. However, the surgical prognosis of patients with MR-negative FCD is unknown. We aimed to evaluate the long-term surgical outcomes and prognostic factors in MR-negative FCD patients through comprehensive presurgical data. Methods: We retrospectively reviewed data from 719 drug-resistant epilepsy patients who underwent resective surgery and selected cases in which surgical specimens were pathologically confirmed as FCD Type I or II. If the epileptogenic focus and surgical specimens were obtained from brain areas with a normal MRI appearance, they were classified as MR-negative FCD. Surgical outcomes were evaluated at 2 and 5 years, and clinical, neurophysiological, and neuroimaging data of MR-negative FCD were compared to those of MR-positive FCD. Results: Finally, 47 MR-negative and 34 MR-positive FCD patients were enrolled in the study. The seizure-free rate after surgery (Engel classification I) at postoperative 2 year was 59.5% and 64.7% in the MR-negative and positive FCD groups, respectively (p = 0.81). This rate decreased to 57.5% and 44.4% in the MR-negative and positive FCD groups (p = 0.43) at postoperative 5 years. MR-negative FCD showed a higher proportion of FCD type I (87.2% vs. 50.0%, p = 0.001) than MR-positive FCD. Unilobar cerebral perfusion distribution (odds ratio, OR 5.41) and concordance of interictal epileptiform discharges (OR 5.10) were significantly associated with good surgical outcomes in MR-negative FCD. Conclusion: In this study, MR-negative and positive FCD patients had a comparable surgical prognosis, suggesting that comprehensive presurgical evaluations, including multimodal neuroimaging studies, are crucial for obtaining excellent surgical outcomes even in epilepsy patients with MR-negative FCD. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is thought to be caused by witchcraft, evil spirit, and God's punishment for sins in many developing countries. As a result, people with epilepsy and their families usually suffer from stigma, discrimination, depression, and other psychiatric problems. Thus, this study aimed to assess the quality of life and its associated factors among epileptic patients attending public hospitals in North Wollo Zone, Northeast Ethiopia. Methods: An institution-based cross-sectional study design was employed in this study. A simple random sampling technique was utilized. Health-related quality of life was measured based on the total score of the Quality of Life in Epilepsy Inventory (QOLIE-31) instrument. Data were entered into Epi-data 3.1 statistical package and exported to SPSS Version 20 for further analysis. Linear regression models were used to assess the relationship between quality of life and the independent variables. Statistically significant values were declared at a P-value of < 0.05. Results: A total of 395 patients participated in the study making the response rate 98.5%. The mean age of the participants was 32.39 ±10.71 years. More than half, 199 (50.4%) of epileptic patients had an overall weighted average health related quality of life score of mean and above. Male sex (B = 4.34, 95%CI, 0.41, 8.27, P = 0.03), higher educational status (B = 7.18, 95%CI, 1.39, 13.00, P = 0.015) and age at onset of epilepsy (B = 0.237, 95%CI, 0.02, 0.45, P = 0.035) were associated with increased health related quality of life score. On the other hand, family history of epilepsy (B = -4.78, 95%CI,-9.24,-0.33, P = 0.035), uncontrolled seizure (B = -11.08, 95%CI,-15.11,-7.05, P < 0.001), more than 5 pre-treatment number of seizures (B = -4.86, 95%CI,-8.91,-0.81, P = 0.019), poor drug adherence (B = -11.65, 95%CI,-16.06,-7.23, P < 0.001), having moderate (B = -4.526, 95%CI,-8.59,-0.46, P = 0.029) to sever (B = -12.84, 95%CI,-18.30,-7.37, P < 0.001) anxiety and depression, believing that epilepsy is caused by evil spirit (B = -7.04, 95%CI,-11.46,-2.61, P = 0.002), drinking alcohol (B = -5.42, 95%CI,-10.72,-0.13, P = 0.045), and having other co-morbidities (B = -9.35, 95%CI,-14.35,-4.36, P < 0.001) were significantly negatively associated with the health related quality of life score among epileptic patients. Conclusions: Only around half of the epileptic patients have a good health-related quality of life. In addition, multiple variables including family history, uncontrolled seizure, and poor drug adherence were associated with quality of life among epileptic patients. Hence, targeting these variables in epilepsy management is recommended. [ABSTRACT FROM AUTHOR]

Background: Evidence from high-income countries demonstrates that co-morbid mental disorders in people with epilepsy adversely affect clinical and social outcomes. However, evidence from low-income countries is lacking. The objective of this study was to measure the association between co-morbid mental disorders and quality of life and functioning in people with epilepsy. Methods: A facility-based, community ascertained cross-sectional survey was carried out in selected districts of the Gurage Zone, Southern Ethiopia. Participants were identified in the community and referred to primary health care (PHC) clinics. Those diagnosed by PHC workers were recruited. Co-morbid mental disorders were measured using a standardised, semi-structured clinical interview administered by mental health professionals. The main outcome, quality of life, was measured using the Quality of Life in Epilepsy questionnaire (QOLIE-10p). The secondary outcome, functional disability, was assessed using the 12-item World Health Organization Disability Assessment Schedule (WHODAS-2). Results: The prevalence of comorbid mental disorders was 13.9%. Comorbid mental disorders were associated with poorer quality of life (Adjusted (Adj.) β -13.27; 95% CI -23.28 to-3.26) and greater disability (multiplier of WHODAS-2 score 1.62; 95% CI 1.05, 2.50) after adjusting for hypothesised confounding factors. Low or very low relative wealth (Adj. β = -12.57, 95% CI -19.94 to-5.20), higher seizure frequency (Adj.β coef. = -1.92, 95% CI -2.83 to -1.02), and poor to intermediate social support (Adj. β coef. = -9.66, 95% CI -16.51 to -2.81) were associated independently with decreased quality of life. Higher seizure frequency (multiplier of WHODAS-2 score 1.11; 95% CI 1.04, 1.19) was associated independently with functional disability. Conclusion: Co-morbid mental disorders were associated with poorer quality of life and impairment, independent of level of seizure control. Integrated and comprehensive psychosocial care is required for better health and social outcomes of people with epilepsy. [ABSTRACT FROM AUTHOR]

A major source of epilepsy is Neurocysticercosis (NCC), caused by Taenia solium infection. Solitary cysticercus granuloma (SCG), a sub-group of NCC induced epilepsy, is the most common form of NCC in India. Current diagnostic criteria for SCG epilepsy require brain imaging which may not be available in communities where the disease is endemic. Identification of serum changes and potential biomolecules that could distinguish SCG epilepsy from idiopathic generalized epilepsy (IE), without the initial need for imaging, could assist in disease identification, understanding, and treatment. The objective here was to investigate, using mass spectrometry (MS), sera biomolecule differences between patients with SCG epilepsy or IE to help distinguish these disorders based on physiological differences, to understand underlying phenotypes and mechanisms, and to lay ground work for future therapeutic and biomarker analyses. Sera were obtained from patients with SCG or IE (N = 29 each group). Serum mass peak profiling was performed with electrospray ionization (ESI) MS, and mass peak area means in the two groups were compared using leave one [serum sample] out cross validation (LOOCV). Serum LOOCV analysis identified significant differences between SCG and IE patient groups (p = 10−20), which became non-significant (p = 0.074) when the samples were randomly allocated to the groups and reanalyzed. Tandem MS/MS peptide analysis of serum mass peaks from SCG or IE patients was performed to help identify potential peptide/protein biochemical and phenotypic changes involving these two forms of epilepsy. Bioinformatic analysis of these peptide/protein changes suggested neurological, inflammatory, seizure, blood brain barrier, cognition, ion channel, cell death, and behavior related biochemical systems were being altered in these disease states. This study provides groundwork for aiding in distinguishing SCG and IE patients in minimally invasive, lower-cost manners, for improving understanding of underlying epilepsy mechanisms, and for further identifying discriminatory biomarkers and potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Non-adherence to anti-seizure medication (ASM) therapy is an important contributing factor to the higher mortality rate and treatment failure of epilepsy. This study aimed to determine the rate and factors associated with non-adherence to ASM therapy through the WHO five dimensions of medication adherence framework. Methods: We conducted a cross-sectional study at an outpatient Neurology Clinic of a tertiary government hospital in Malaysia. Between March and July 2019, we identified 217 patients with a confirmed diagnosis of epilepsy, receiving oral ASM therapy and able to administer their medications. We performed a semi-structured interview to gather information on sociodemographic background, clinical and medication history, and perceptions on healthcare services. Adherence to ASM therapy was evaluated using the Medication Compliance Questionnaire (MCQ). Patient's illness perception was assessed by the Brief Illness Perception Questionnaire (B-IPQ). Results: 208 patients participated in this study. The median age of the study participants was 35 years (IQR 26–44). 58.2% were females and majority, 55.8%, were from the Malay ethnic group. Based on the MCQ scoring, 89 patients (42.8%) were non-adherent. Multiple logistic regression demonstrated that being employed or students (adjusted odds ratio [aOR] 2.26, 95%CI: 1.19–4.29 p = 0.012) and having an average or below average perceived access to pharmacy services (aOR 2.94, 95%CI: 1.38–6.24, p = 0.005) were significant contributors to non-adherence. Conclusion: Being employed or students and having an average or below average perceived access to pharmacy services were associated with ASM non-adherence Efforts to improve ASM adherence should adopt a comprehensive approach considering the success of adherence is contingent on the interrelationship of multiple dimensions. [ABSTRACT FROM AUTHOR]

Background: Patients with epilepsy (PwE) have an increased risk of active and lifetime depression. Two in 10 patients experience depression. Lack of trained psychiatric staff in low- and middle-income countries (LMIC) creates a need for screening tools that enable detection of depression in PwE. We describe the translation, validity and reliability assessment of the Patient Health Questionnaire-9 (PHQ-9) as a screening tool for depression among PwE in Rwanda. Method: PHQ-9 was translated to Kinyarwanda using translation-back translation and validated by a discussion group. For validation, PwE of ≥15 years of age were administered the PHQ-9 and Hamilton Depression Rating Scale (HDRS) by trained psychiatry staff at Visit 1. A random sample of 20% repeated PHQ-9 and HDRS after 14 days to assess temporal stability and intra-rater reliability. Internal structure, reliability and external validity were assessed using confirmatory factor analysis, reliability coefficients and HDRS-correlation, respectively. Maximal Youden's index was considered for cut-offs. Results: Four hundred and thirty-four PwE, mean age 30.5 years (SD ±13.3), were included of whom 33.6%, 37.9%, 13.4%, and 15.1% had no, mild, moderate and severe depression, respectively. PHQ-9 performed well on a one-factor model (unidimensional model), with factor loadings of 0.63–0.86. Reliability coefficients above 0.80 indicated strong internal consistency. Good temporal stability was observed (0.79 [95% CI: 0.68–0.87]). A strong correlation (R = 0.66, p = 0.01) between PHQ-9 and HDRS summed scores demonstrated robust external validity. The optimal cut-off for the PHQ-9 was similar (≥5) for mild and moderate depression and ≥7 for severe depression. Conclusion: PHQ-9 validation in Kinyarwanda creates the capacity to screen PwE in Rwanda at scores of ≥5 for mild or moderate and ≥7 for severe depression. The availability of validated tools for screening and diagnosis for depression is a forward step for holistic care in a resource-limited environment. [ABSTRACT FROM AUTHOR]

Pharmacotherapy with two antiepileptic drugs in combination is usually prescribed to epilepsy patients with refractory seizures. The choice of antiepileptic drugs in combination should be based on synergistic cooperation of the drugs with respect to suppression of seizures. The selection of synergistic interactions between antiepileptic drugs is challenging issue for physicians, especially, if 25 antiepileptic drugs are currently available and approved to treat epilepsy patients. The aim of this study was to determine all possible interactions among 5 second-generation antiepileptic drugs (gabapentin (GBP), lacosamide (LCM), levetiracetam (LEV), pregabalin (PGB) and retigabine (RTG)) in the 6-Hz corneal stimulation-induced seizure model in adult male albino Swiss mice. The anticonvulsant effects of 10 various two-drug combinations of antiepileptic drugs were evaluated with type I isobolographic analysis associated with graphical presentation of polygonogram to visualize the types of interactions. Isobolographic analysis revealed that 7 two-drug combinations of LEV+RTG, LEV+LCM, GBP+RTG, PGB+LEV, GBP+LEV, PGB+RTG, PGB+LCM were synergistic in the 6-Hz corneal stimulation-induced seizure model in mice. The additive interaction was observed for the combinations of GBP+LCM, GBP+PGB, and RTG+LCM in this seizure model in mice. The most beneficial combination, offering the highest level of synergistic suppression of seizures in mice was that of LEV+RTG, whereas the most additive combination that protected the animals from seizures was that reporting additivity for RTG+LCM. The strength of interaction for two-drug combinations can be arranged from the synergistic to the additive, as follows: LEV+RTG > LEV+LCM > GBP+RTG > PGB+LEV > GBP+LEV > PGB+RTG > PGB+LCM > GBP+LCM > GBP+PGB > RTG+LCM. [ABSTRACT FROM AUTHOR]

Background: Common mental illness has a substantial impact on seizure control and negatively affects the overall quality of life among individuals with epilepsy. However, there is a dearth of studies that examined the associated factors of common mental illness among epilepsy patients in Ethiopia, particularly in the study area. This study aimed to assess the magnitude and factors associated with common mental disorders in epilepsy patients who attended government health institutions in Bahir Dar city, Ethiopia. Method: Health institution based cross-sectional study was conducted using a systematic sampling technique among people living with epilepsy in Bahir Dar City Administration. Common mental illness was assessed using a self-reporting questionnaire and a semi-structured questionnaire was employed to collect data on socio-demographic and clinical related characteristics. Data were analyzed using descriptive statistics, univariate logistic regression, and multivariable logistic regression. Results: The magnitude of comorbid common mental illness among people living with epilepsy was found 35.4%. High magnitude of common mental illness was reported among females (39.9%) when compared to males (32.3%). The most prevalent common mental disorders symptoms include being worried, unhappy feeling, trouble thinking clearly, and difficult to enjoy daily activities. Family history of epilepsy, frequent seizures attacks, side effects of antiepileptic drugs, lack of social support and not adherent to antiepileptic drugs were factors associated with common mental illness. Conclusions: Common mental illness was found to be prevalent among people living with epilepsy. Therefore, it is recommended that great attention should be given to mental illness besides controlling seizure attacks. [ABSTRACT FROM AUTHOR]

Background: Health‐related quality of life (HRQOL) is used as a measure of treatment outcomes, in addition to seizure control. Hence, the study was aimed to assess HRQOL and its determinants among adult patients with epilepsy (PWE). Method: A hospital-based cross-sectional study was conducted from April 20 to June 27/2019, through patient interviews and patient's chart review (medication and clinical information). Data were analyzed using SPSS version 20. The psychometric property was done using Cronbach's alpha test value of >0.7 as accepted internal consistency and Kaiser-Meyer-Olkin (KMO) measure of sample size adequacy value of ≥0.5 as acceptable construct validity, for Afaan Oromo version questionnaire. Multivariate linear logistic regression analysis was done to find predictors for the HRQOL score. Results: Of 121 PWE included in the study, 24.4% had overall poor HRQOL with the overall mean ±SD score of 56.42±10.96. The predictors for low overall HRQOL score were: presence of co-morbidity (B = -5.620, SE = 1.531, p<0.0001, 95% C.I = -8.656 to -2.584), uncontrolled seizure for at least 2 years (B = -4.239, SE = 1.296, p = 0.001, 95% C.I = -6.809 to -1.670), divorced (B = -8.423, SE = 2.241, p<0.0001, 95%C.I = -12.867 to -3.978) relative to married, and no education (B = -8.715, SE = -8.15, SE = 2.604, p = 0.001, 95%C.I = -9.648 to -1.316) relative to who had level of education above tertiary. In addition, uncontrolled seizure (irrespective of time since seizure-free) (B = -10.083, SE = 2.104, p<0.0001, 95%C.I = -14.256 to -5.910), being widowed (B = -9.300, SE = 3.594, p = 0.011, 95%C.I = -16.429–2.170) relative to married and being illiterate/no education (B = -13.004, SE = 3.910, p = 0.001, 95%C.I = -20.760 to -5.248) relative to educational level of tertiary and above were found to be the strongest negative predictors of HRQOL of physical health. Moreover, uncontrolled seizure (irrespective of time since seizure-free) (B = -12.668, SE = 2.019, p<0.0001, 95%C.I = -16.671 to -8.664) and being divorced (B = -10.153, SE = 3.228, p = 0.002, 95%C.I = -16.556 to -3.751) compared to married were strong predictors for low HRQOL score of psychological health. Absence of Poly-pharmacy (B = 9.050, SE = 3.027, P = 0.003, 95%C.I = 3.047 to 15.054), being single (B = -9.551, SE = 2.095, p<0.0001, 95%C.I = -14.419 to -4.683), and divorced (B = -11.022, SE = 3.351, P = 0.001, 95%C.I = -17.668 to -4.376) relative to married were found to be strong predictors for HRQOL score of social health. Moreover, low HRQOL score of environmental health was predicted by rural residence (B = -5.795, SE = 2.101, p = 0.007, 95%C.I = -9.962 to -1.628), co-morbidity (B+ -4.230, SE = 2.125, p = 0.049, 95%C.I = -8.444 to -0.015) & uncontrolled seizure irrespective of time since seizure-free (B = -6.907, SE = 1.945, p = 0.001, 95%C.I = -10.765 to -3.049) and uncontrolled seizure of at least 2 years (B = -4.520, SE = 1.798, p = 0.014, 95%C.I = -8.088 to -0.953). Conclusions: The majority of the study participants had a good overall HRQOL. In general, a low level of HRQOL score was significantly associated with the marital status of single/widowed/divorced, low level of education, low level of monthly income, co-morbidity, uncontrolled seizure, and poly-pharmacy; irrespective of HRQOL domains. Therefore, it is required to improve HRQOL, by avoiding modifiable factors for PWE to achieve the optimum HRQOL. [ABSTRACT FROM AUTHOR]

Quantitative MRI methods have recently gained extensive interest and are seeing substantial developments; however, their application in single patient vs control group comparisons is often limited by inherent statistical difficulties. One such application is detecting malformations of cortical development (MCDs) behind drug resistant epilepsies, a task that, especially when based solely on conventional MR images, may represent a serious challenge. We aimed to develop a novel straightforward voxel-wise evaluation method based on the Mahalanobis-distance, combining quantitative MRI data into a multidimensional parameter space and detecting lesion voxels as outliers. Simulations with standard multivariate Gaussian distribution and resampled DTI-eigenvalue data of 45 healthy control subjects determined the optimal critical value, cluster size threshold, and the expectable lesion detection performance through ROC-analyses. To reduce the effect of false positives emanating from registration artefacts and gyrification differences, an automatic classification method was applied, fine-tuned using a leave-one-out strategy based on diffusion and T1-weighted data of the controls. DWI processing, including thorough corrections and robust tensor fitting was performed with ExploreDTI, spatial coregistration was achieved with the DARTEL tools of SPM12. Additional to simulations, clusters of outlying diffusion profile, concordant with neuroradiological evaluation and independent calculations with the MAP07 toolbox were identified in 12 cases of a 13 patient example population with various types of MCDs. The multidimensional approach proved sufficiently sensitive in pinpointing regions of abnormal tissue microstructure using DTI data both in simulations and in the heterogeneous example population. Inherent limitations posed by registration artefacts, age-related differences, and the different or mixed pathologies limit the generalization of specificity estimation. Nevertheless, the proposed statistical method may aid the everyday examination of individual subjects, ever so more upon extending the framework with quantitative information from other modalities, e.g. susceptibility mapping, relaxometry, or perfusion. [ABSTRACT FROM AUTHOR]

Objective: To compare by 7 Tesla (7T) magnetic resonance imaging (MRI) in patients with focal epilepsy who have non-lesional clinical MRI scans with healthy controls. Methods: 37 patients with focal epilepsy, based on clinical and electroencephalogram (EEG) data, with non-lesional MRIs at clinical field strengths and 21 healthy controls were recruited for the 7T imaging study. The MRI protocol consisted of high resolution T1-weighted, T2-weighted and susceptibility weighted imaging sequences of the entire cortex. The images were read by two neuroradiologists, who were initially blind to clinical data, and then reviewed a second time with knowledge of the seizure onset zone. Results: A total of 25 patients had findings with epileptogenic potential. In five patients these were definitely related to their epilepsy, confirmed through surgical intervention, in three they co-localized to the suspected seizure onset zone and likely caused the seizures. In seven patients the imaging findings co-localized to the suspected seizure onset zone but were not the definitive cause, and ten had cortical lesions with epileptogenic potential that did not localize to the suspected seizure onset zone. There were multiple other findings of uncertain significance found in both epilepsy patients and healthy controls. The susceptibility weighted imaging sequence was instrumental in guiding more targeted inspection of the other structural images and aiding in the identification of cortical lesions. Significance: Information revealed by the improved resolution and enhanced contrast provided by 7T imaging is valuable in noninvasive identification of lesions in epilepsy patients who are non-lesional at clinical field strengths. [ABSTRACT FROM AUTHOR]

Mutations in the SCN1A gene, which encodes for the voltage-gated sodium channel NaV1.1, cause Dravet syndrome, a severe developmental and epileptic encephalopathy. Genetic testing of this gene is recommended early in life. However, predicting the outcome of de novo missense SCN1A mutations is difficult, since milder epileptic syndromes may also be associated. In this study, we correlated clinical severity with functional in vitro electrophysiological testing of channel activity and bioinformatics prediction of damaging mutational effects. Three patients, bearing the mutations p.Gly177Ala, p.Ser259Arg and p.Glu1923Arg, showed frequent intractable seizures that had started early in life, with cognitive and behavioral deterioration, consistent with classical Dravet phenotypes. These mutations failed to produce measurable sodium currents in a mammalian expression system, indicating complete loss of channel function. A fourth patient, who harbored the mutation p.Met1267Ile, though presenting with seizures early in life, showed lower seizure burden and higher cognitive function, matching borderland Dravet phenotypes. In correlation with this, functional analysis demonstrated the presence of sodium currents, but with partial loss of function. In contrast, six bioinformatics tools for predicting mutational pathogenicity suggested similar impact for all mutations. Likewise, homology modeling of the secondary and tertiary structures failed to reveal misfolding. In conclusion, functional studies using patch clamp are suggested as a prognostic tool, whereby detectable currents imply milder phenotypes and absence of currents indicate an unfavorable prognosis. Future development of automated patch clamp systems will facilitate the inclusion of such functional testing as part of personalized patient diagnostic schemes. [ABSTRACT FROM AUTHOR]

Objective: The aims of this study were to identify the influencing factors such as gender, age, dose and combinations of other antiepileptic drugs (AEDs), especially in triple combinations on the pharmacokinetic of Lamotrigine (LTG) in epilepsy patients of Northwest Chinese Han population. Methods: Data of the LTG concentration and clinical information were analyzed retrospectively from a therapeutic drug monitoring (TDM) database at the Clinical Pharmacy Laboratory of Xi’an Central Hospital between January 1, 2016 and January 1, 2018. The independent-sample t-test, one-way ANOVA analysis and Bonferroni and Tamhane T3 post-hoc test, the stepwise multivariate regression analysis were adopted by IBM SPSS, version 22.0. Results: 226 serum samples met the inclusion criteria and were evaluated. The mean LTG serum concentration was 5.48±3.83 μg/mL. There were no gender differences (P = 0.64), and there were no significant effects by age on LTG serum concentration after age stratification (3–14 years old, 14-45 years old, 45–59 years old) (P = 0.05). Multiple regression analysis showed that the daily LTG dose and co-administration of other AEDs significantly affected LTG serum concentrations. Combination with enzyme-inducer AEDs, the mean steady-state LTG concentration could be decreased by 30.73% compared with LTG monotherapy. Among enzyme-inducer AEDs, particularly strong inducer Carbamazepine (CBZ) could decrease the mean LTG concentration by 53.65%, but weak inducer AEDs such as Oxcarbazepine (OXC) and Topiramate (TPM) had no effect, Valproic acid (VPA) could increase the mean LTG concentration by 93.95%, and the inducer only partially compensated for the inhibitory effect of VPA in triple combination. Conclusions: There were no significant gender and age effects, but the LTG daily dose and co-administration of other AEDs significantly affected LTG serum concentration. Combination with enzyme-inducer AEDs, especially CBZ could significantly decrease LTG serum concentrations, VPA could significantly increase LTG serum concentrations, and the inducer only partially compensated for the inhibitory effect of VPA in triple combination. In the clinical setting, these findings can help to estimate LTG concentrations and adjust dosage and evaluate adverse drug reactions. [ABSTRACT FROM AUTHOR]

Objective: The intracarotid amobarbital procedure (IAP) is the current “gold standard” in the preoperative assessment of language lateralization in epilepsy surgery candidates. It is, however, invasive and has several limitations. Here we tested a simple noninvasive language lateralization test performed with magnetoencephalography (MEG). Methods: We recorded auditory MEG responses to pairs of vowels and pure tones in 16 epilepsy surgery candidates who had undergone IAP. For each individual, we selected the pair of planar gradiometer sensors with the strongest N100m response to vowels in each hemisphere and—from the vector sum of signals of this gradiometer pair—calculated the vowel/tone amplitude ratio in the left (L) and right (R) hemisphere and, subsequently, the laterality index: LI = (L–R)/(L+R). In addition to the analysis using a single sensor pair, an alternative analysis was performed using averaged responses over 18 temporal sensor pairs in both hemispheres. Results: The laterality index did not correlate significantly with the lateralization data obtained from the IAP. However, an MEG pattern of stronger responses to vowels than tones in the left hemisphere and stronger responses to tones than vowels in the right hemisphere was associated with left-hemispheric language dominance in the IAP in all the six patients who showed this pattern. This results in a specificity of 100% and a sensitivity of 67% of this MEG pattern in predicting left-hemispheric language dominance (p = 0.01, Fisher's exact test). In the analysis using averaged responses over temporal channels, one additional patient who was left-dominant in IAP showed this particular MEG pattern, increasing the sensitivity to 78% (p = 0.003). Significance: This simple MEG paradigm shows promise in feasibly and noninvasively confirming left-hemispheric language dominance in epilepsy surgery candidates. It may aid in reducing the need for the IAP, if the results are confirmed in larger patient samples. [ABSTRACT FROM AUTHOR]

Purpose: One quarter of people with epilepsy have an intellectual disability (ID) and one fifth of people with an ID have epilepsy. Both conditions are associated with higher levels of morbidity, stigma and premature mortality. There have been calls for action to promote more research in this group. We examined if this group are represented adequately in current research. Methods: The proportion of research output in epilepsy conferences and publications relevant to ID and the proportion in ID conferences and publications on epilepsy for 2015–2016 were identified. As the percentage of children in the population with epilepsy is 17%, research output of this group was compared with the ID group. Recognised material was classified based on whether it applied to general epilepsy/ID research, children with epilepsy or people with epilepsy and ID. Data was analysed to determine the proportion of presented research specifically identifying people with epilepsy and ID. Results: Fewer than 2% of presentations at epilepsy conferences specifically related to the ID and epilepsy group compared to 15% relating to children with epilepsy. Similarly only 1.4% of the research presented at major ID conferences related to those with people with epilepsy and ID. About 5% of published research in the field of epilepsy related to those with ID as compared with 24% for children with epilepsy. Twelve percent of published research in ID specifically identified epilepsy. Conclusion: Publications and conference presentations, on the population with epilepsy and comorbid ID is under-represented. Increased research in this area might assist in improving the quality of care for this relatively neglected group. [ABSTRACT FROM AUTHOR]

Genetic heterogeneity of common genetic generalized epilepsy syndromes is frequently considered. The present study conducted a focused analysis of potential candidate or susceptibility genes for common genetic generalized epilepsy syndromes using multi-gene panel testing with next-generation sequencing. This study included patients with juvenile myoclonic epilepsy, juvenile absence epilepsy, and epilepsy with generalized tonic-clonic seizures alone. We identified pathogenic variants according to the American College of Medical Genetics and Genomics guidelines and identified susceptibility variants using case-control association analyses and family analyses for familial cases. A total of 57 patients were enrolled, including 51 sporadic cases and 6 familial cases. Twenty-two pathogenic and likely pathogenic variants of 16 different genes were identified. CACNA1H was the most frequently observed single gene. Variants of voltage-gated Ca2+ channel genes, including CACNA1A, CACNA1G, and CACNA1H were observed in 32% of variants (n = 7/22). Analyses to identify susceptibility variants using case-control association analysis indicated that KCNMA1 c.400G>C was associated with common genetic generalized epilepsy syndromes. Only 1 family (family A) exhibited a candidate pathogenic variant p.(Arg788His) on CACNA1H, as determined via family analyses. This study identified candidate genetic variants in about a quarter of patients (n = 16/57) and an average of 2.8 variants was identified in each patient. The results reinforced the polygenic disorder with very high locus and allelic heterogeneity of common GGE syndromes. Further, voltage-gated Ca2+ channels are suggested as important contributors to common genetic generalized epilepsy syndromes. This study extends our comprehensive understanding of common genetic generalized epilepsy syndromes. [ABSTRACT FROM AUTHOR]

Objective: Despite modern anti-epileptic drug treatment, approximately 30% of epilepsies remain medically refractory and for these patients, epilepsy surgery may be a treatment option. There have been numerous studies demonstrating good outcome of epilepsy surgery in the short to median term however, there are a limited number of studies looking at the long-term outcomes. The aim of this study was to ascertain the long-term outcome of resective epilepsy surgery in a large neurosurgery hospital in the U.K. Methods: This a retrospective analysis of prospectively collected data. We used the 2001 International League Against Epilepsy (ILAE) classification system to classify seizure freedom and Kaplan-Meier survival analysis to estimate the probability of seizure freedom. Results: We included 284 patients who underwent epilepsy surgery (178 anterior temporal lobe resections, 37 selective amygdalohippocampectomies, 33 temporal lesionectomies, 36 extratemporal lesionectomies), and had a prospective median follow-up of 5 years (range 1–27). Kaplan-Meier estimates showed that 47% (95% CI 40–58) remained seizure free (apart from simple partial seizures) at 5 years and 38% (95% CI 31–45) at 10 years after surgery. 74% (95% CI 69–80) had a greater than 50% seizure reduction at 5 years and 70% (95% CI 64–77) at 10 years. Patients who had an amygdalohippocampectomy were more likely to have seizure recurrence than patients who had an anterior temporal lobe resection (p = 0.006) and temporal lesionectomy (p = 0.029). There was no significant difference between extra temporal and temporal lesionectomies. Hippocampal sclerosis was associated with a good outcome but declined in relative frequency over the years. Conclusion: The vast majority of patients who were not seizure free experienced at least a substantial and long-lasting reduction in seizure frequency. A positive long-term outcome after epilepsy surgery is possible for many patients and especially those with hippocampal sclerosis or those who had anterior temporal lobe resections. [ABSTRACT FROM AUTHOR]

Carbon dioxide (CO2) is one of the most commonly used euthanasia agents for mice, yet it is highly aversive and nociceptive. Inert gases are a possible alternative, however there are qualitative reports of seizures resulting from exposure. Here we evaluate epileptiform activity caused by inert gases (N2, He, Ar and Xe) and CO2 in mice chronically instrumented for EEG/EMG undergoing single-gas euthanasia. We found that N2, He and Ar caused epileptiform activity in all animals, CO2 in half of animals and no epileptiform activity produced by Xe. Atmospheric O2 concentrations at epileptiform activity onset were significantly higher for CO2 than for all other gases and occurred soon after loss of motion, whereas N2 and Ar epileptiform activity occurred at cessation of neocortical activity. Helium caused the longest epileptiform activity and these commenced significantly before isoelectric EEG. We did not detect any epileptiform activity during active behaviour. Taken together, these results demonstrate that whilst epileptiform activity from inert gases and particularly Ar and N2 are more prevalent than for CO2, their occurrence at the onset of an isoelectric EEG is unlikely to impact on the welfare of the animal. Epileptiform activity from these gases should not preclude them from further investigation as euthanasia agents. The genesis of epileptiform activity from CO2 is unlikely to result from hypoxia as with the inert gases. Helium caused epileptiform activity before cessation of neocortical activity and for a longer duration and is therefore less suitable as an alternative to CO2. [ABSTRACT FROM AUTHOR]

We investigate how changes in network structure can lead to pathological oscillations similar to those observed in epileptic brain. Specifically, we conduct a bifurcation analysis of a network of two Jansen-Rit neural mass models, representing two cortical regions, to investigate different aspects of its behavior with respect to changes in the input and interconnection gains. The bifurcation diagrams, along with simulated EEG time series, exhibit diverse behaviors when varying the input, coupling strength, and network structure. We show that this simple network of neural mass models can generate various oscillatory activities, including delta wave activity, which has not been previously reported through analysis of a single Jansen-Rit neural mass model. Our analysis shows that spike-wave discharges can occur in a cortical region as a result of input changes in the other region, which may have important implications for epilepsy treatment. The bifurcation analysis is related to clinical data in two case studies. [ABSTRACT FROM AUTHOR]

Sudden unexpected death in epilepsy is an unpredicted condition in patients with a diagnosis of epilepsy, and autopsy does not conclusively identify cause of death. Although the pathophysiological mechanisms that underlie this entity remain unknown, the fact that epilepsy can affect cardiac function is not surprising. The genetic factors involving ion channels co-expressed in the heart and brain and other candidate genes have been previously described. In the present study, 20 epilepsy patients with personal or family history of heart rhythm disturbance/cardiac arrhythmias/sudden death were sequenced using a custom re-sequencing panel. Twenty-six relatives were genetically analysed to ascertain the family segregation in ten individuals. Four subjects revealed variants with positive genotype-phenotype segregation: four missense variants in the CDKL5, CNTNAP2, GRIN2A and ADGRV1 genes and one copy number variant in KCNQ1. The potential pathogenic role of variants in new candidate genes will need further studies in larger cohorts, and the evaluation of the potential pathogenic role in the cardio-cerebral mechanisms requires in vivo/in vitro studies. In addition to family segregation, evaluation of the potential pathogenic roles of these variants in cardio-cerebral mechanisms by in vivo/in vitro studies should also be performed. The potential pathogenic role of variants in new candidate genes will need further studies in larger cohorts. [ABSTRACT FROM AUTHOR]

Pediatric epilepsies are a group of disorders with a broad phenotypic spectrum that are associated with great genetic heterogeneity, thus making sequential single-gene testing an impractical basis for diagnostic strategy. The advent of next-generation sequencing has increased the success rate of epilepsy diagnosis, and targeted resequencing using genetic panels is the a most cost-effective choice. We report the results found in a group of 87 patients with epilepsy and developmental delay using targeted next generation sequencing (custom-designed Haloplex panel). Using this gene panel, we were able to identify disease-causing variants in 17 out of 87 (19.5%) analyzed patients, all found in known epilepsy-associated genes (KCNQ2, CDKL5, STXBP1, SCN1A, PCDH19, POLG, SLC2A1, ARX, ALG13, CHD2, SYNGAP1, and GRIN1). Twelve of 18 variants arose de novo and 6 were novel. The highest yield was found in patients with onset in the first years of life, especially in patients classified as having early-onset epileptic encephalopathy. Knowledge of the underlying genetic cause provides essential information on prognosis and could be used to avoid unnecessary studies, which may result in a greater diagnostic cost-effectiveness. [ABSTRACT FROM AUTHOR]