Patients With Epilepsy Research Articles

Imaging blood-brain barrier dysfunction in drug-resistant epilepsy: A multi-center feasibility study.

Blood-brain barrier dysfunction (BBBD) has been linked to various neurological disorders, including epilepsy. This study aims to utilize dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to identify and compare brain regions with BBBD in patients with epilepsy (PWE) and healthy individuals. We scanned 50 drug-resistant epilepsy (DRE) patients and 58 control participants from four global specialized epilepsy centers using DCE-MRI. The presence and extent of BBBD were analyzed and compared between PWE and healthy controls. Both greater brain volume and higher number of brain regions with BBBD were significantly present in PWE compared to healthy controls (p < 10-7). No differences in total brain volume with BBBD were observed in patients diagnosed with either focal seizures or generalized epilepsy, despite variations in the affected regions. Overall brain volume with BBBD did not differ in PWE with MRI-visible lesions compared with non-lesional cases. BBBD was observed in brain regions suspected to be related to the onset of seizures in 82% of patients (n = 39) and was typically identified in, adjacent to, and/or in the same hemisphere as the suspected epileptogenic lesion (n = 10). These findings are consistent with pre-clinical studies that highlight the role of BBBD in the development of DRE and identify microvascular stabilization as a potential therapeutic strategy.

Evaluation of self-stigma in patients with epilepsy: Validation of the self-stigma scale to Spanish (ESSS-S).

The Epilepsy Self-Stigma Scale (ESSS) has been developed in Japan for patients with epilepsy (PWE). We aimed to validate the scale in Spanish and examine its validity and reliability. The transcultural adaptation of the ESSS was conducted using translation and back-translation, along with pilot testing and an expert panel review. An online questionnaire was used to assess construct validity, criterion validity, and internal consistency. A total of 260 out of 628 participants completed the questionnaires. We found a two-factor structure that explained 61.3% of the total variance: factor 1 "self-perceived discrimination" with a Cronbach's alpha of 0.80, and factor 2 "social isolation" with a Cronbach's alpha of 0.75. The reliability of overall ESSS-S 8-item scores was high (Cronbach's alpha = 0.74). Convergent validity was tested and demonstrated a significant correlation. P. Self-perceived discrimination scores were associated with higher anxiety and depression scores (r = 0.53/0.54; p < 0.001), lower self-esteem (-0.53; p < 0.001), and lower quality of life (r = -0.66; p < 0.001). Social isolation scores were associated with higher anxiety and depression scores (r = 0.41/0.33; p < 0.001), lower self-esteem (-0.34; p < 0.001), and lower quality of life (r = -0.35; p < 0.001). Temporal reliability was also tested, showing a test-retest ICC of 0.87. The mean self-stigma score in the Spanish population was 17.68 ± 5.45 out of 32 points. Invariance across gender and age groups indicated that there are no systematic response biases by gender or age, so stratified scores could be related to other constructs. The Spanish version of ESSS (ESSS-S) is a valid and reliable tool for the assessment of self-stigma in PWE among Spanish speakers. This study aimed to validate the Epilepsy Self-Stigma Scale (ESSS) for Spanish speakers (ESSS-S). We conducted transcultural adaptation of the scale. ESSS-S showed high reliability and strong validity, correlating with higher anxiety and depression, lower self-esteem, and quality of life. ESSS-S is a reliable and valid tool for assessing self-stigma in Spanish-speaking people with epilepsy.

The bidirectional role of music effect in epilepsy: Friend or foe?

Epilepsy is a prevalent neurological disease that impacts around 70 million individuals globally. Anti-seizure medications (ASMs) are the first choice for clinicians to control unprovoked epileptic seizures. Although more than 30 ASMs are available in the market, patients with epilepsy (PWEs) still show poor responses to adequate drug treatment. Meanwhile, long-term medications not only bring heavy financial burdens but also lead to undesirable side effects. Music, a ubiquitous art form throughout human history, has been confirmed as therapeutically effective in various neurological conditions, including epilepsy. This alternative therapy offers convenience and a relatively safe approach to alleviating epileptic symptoms. Paradoxically, besides anti-convulsant effect, some particular music would cause seizures inversely, indicating the pro-convulsant effect of it. Considering that investigating the impact of music on epilepsy emerges as a compelling subject. In this review, we tried to present the following sections of content on this topic. Initially, we overviewed the impact of music on the brain and the significant progress of music therapy in central neurological disorders. Afterward, we classified the anti-convulsant and pro-convulsant effects of music in epilepsy, relying on both clinical and laboratory evidences. Finally, possible mechanisms and neural basis of the music effect were concluded, and the translational potentials and some future outlooks about the music effect in epilepsy were proposed. PLAIN LANGUAGE SUMMARY: Epilepsy is an extremely severe neurological disorder. Although anti-seizure medications are preferred choice to control seizures, the efficacy is not satisfied due to the tolerance. Anecdotal music effect had been deemed functional diversity but not clarified on epilepsy, pro-convulsive, or anti-convulsive. Here, we reviewed this interesting but puzzling topic, as well as illustrating the potential mechanisms and its translational potential.

Association of baseline sleep duration and sleep quality with seizure recurrence in newly treated patients with epilepsy.

Although sleep duration and sleep quality are considered to be significant factors associated with epilepsy and seizure risk, findings are inconsistent, and their joint association remains uncertain. This study aimed to determine independent and joint associations of these two modifiable sleep features with seizure recurrence risk in newly treated patients with epilepsy (PWE). This is a prospective cohort study of newly treated PWE at a comprehensive epilepsy center in northeast China between June 2020 and December 2023. Self-reported sleep duration and sleep quality were collected at baseline. All patients were followed for 12 months for recurrent seizures. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) of seizure recurrence. Models fitted with restricted cubic spline were conducted to test for linear and nonlinear shapes of each association. A total of 209 patients were included, and 103 experienced seizure recurrence during follow-up. Baseline short sleep was significantly associated with greater risk of seizure recurrence (adjusted HR = 2.282, 95% confidence interval [CI] = 1.436-3.628, p < .001). Sleep duration (h/day) and recurrent seizure risk showed a significant nonlinear U-shaped association, with a nadir at 8 h/day. Baseline poor sleep quality was significantly associated with greater risk of seizure recurrence (adjusted HR = 1.985, 95% CI = 1.321-2.984, p < .001). Pittsburgh Sleep Quality Index score and seizure recurrence risk exhibited a positive linear association. Participants with a combination of poor quality-short sleep showed the highest risk of seizure recurrence (adjusted HR = 3.13, 95% CI = 1.779-5.507, p < .001) compared to the referent good quality-intermediate sleep group. Baseline sleep duration and sleep quality were independently and jointly associated with risk of seizure recurrence in newly treated PWE. Our results point to an important potential role of baseline sleep duration and sleep quality in shaping seizure risk.

Screening for depression in patients with epilepsy: same questions but different meaning to different patients.

Patient-reported outcome measures (PROMs) such as the Neurological Disorders Depression Inventory in Epilepsy (NDDI-E), a 6-item epilepsy-specific PROM, is used to screen for major depressive disorder symptoms for patients with epilepsy (PWE). The validity and interpretation of PROMs can be affected by differential item functioning (DIF), which occurs when subgroups of patients with the same underlying health status respond to and interpret questions about their health status differently. This study aims to determine whether NDDI-E items exhibit DIF and to identify subgroups of PWE that exhibit DIF in NDDI-E items. Data were from the Calgary Comprehensive Epilepsy Program database, a clinical registry of adult PWE in Calgary, Canada. A tree-based partial credit model based on recursive partitioning (PCTree) was used to identify subgroups that exhibit DIF on NDDI-E items using patients' characteristics as covariates. Differences in the identified subgroups were characterized using multinomial logistic regression. Of the 1,576 patients in this cohort, 806 (51.1%) were female, and the median age was 38.0 years. PCTree identified four patient subgroups defined by employment status, age, and sex. Subgroup 1 were unemployed patients ≤ 26 years old, subgroup 2 were unemployed patients > 26 years, subgroup 3 were employed females, while subgroup 4 were employed male patients. The subgroups exhibited significant differences on education level, comorbidity index scores, marital status, type of epilepsy, and driving status. PWE differed in their interpretation and responses to questions about their depression symptoms, and these differences were a function of sociodemographic and clinical characteristics.

Factors affecting psychiatrist hesitation towards epilepsy care and care for patients with epilepsy transitioning from pediatric to adult care: A survey by the Japanese Society of General Hospital Psychiatry

ObjectiveThis study was undertaken by the Epilepsy Subcommittee of the Japanese Society of General Hospital Psychiatry (JSGHP) to explore the challenges faced by psychiatrists in treating epilepsy and the difficulties encountered during the transition of patients with epilepsy (PWE) from pediatric to adult care. MethodsAn online survey targeting 1,980 JSGHP-affiliated psychiatrists was conducted from May to July 2022. The participants were asked to complete a questionnaire on epilepsy care. We analyzed the factors associated with participant hesitancy to treat epilepsy and their professional characteristics. ResultsResponses were obtained from 545 of the 1,980 solicited psychiatrists (response rate: 27.5 %). The mean number of years of clinical experience in psychiatry was 20.9 ± 10.3 years. A majority of the psychiatrists were hesitant toward treating epilepsy (89.2 %) and managing the transition of PWE from pediatric services to adult care (83.3 %). Logistic regression analysis showed that the absence of hesitation toward epilepsy treatment was significantly associated with years of clinical experience in psychiatry (OR: 1.05, p = 0.002), being a board-certified epileptologist (OR: 4.36, p = 0.037), having colleagues who are specialists in epilepsy care that may be consulted in the workplace (OR: 2.12, p = 0.027), and general confidence in managing PWE transition from pediatric to adult care (OR 3.54, p < 0.001). Confidence in managing the transition was positively correlated with being a board-certified psychiatrist of the Japanese Society of Psychiatry and Neurology (OR: 4.55, p = 0.048), being a board-certified psychiatrist of the JSGHP (OR: 1.75, p = 0.034), treating six or more PWE per month (OR: 3.54; 95 % CI, p < 0.001), and overall confidence in treating epilepsy (OR: 3.38, p < 0.001). ConclusionsAlleviation of reluctance to providing epilepsy care and managing the process of transition are correlated; however, the factors influencing each are distinct. To reduce resistance to epilepsy treatment, enhancing the knowledge of epilepsy and creating an environment conducive to consultations are essential. Improving transition-related outcomes, having substantial psychiatric expertise, and increasing opportunities to treat PWE are of great significance. The integration of these approaches may enable psychiatrists to alleviate hesitancy towards epilepsy care and enhance both treatment and transitional care modalities.

Seizure-Related Injuries among Patients with Epilepsy at the Douala General Hospital, Cameroon: A Retrospective Cohort Study

Abstract Background Seizures can lead to injuries in patients with epilepsy (PWE). This study seeks to determine the 1-year incidence, types, and associated factors of seizure-related injuries in PWE compared with that of patients without epilepsy. Methods A retrospective cohort study was carried out at the Douala General Hospital, Douala, Cameroon. Patients with active epilepsy within the past 5 years were compared to patients without epilepsy after matching them by age and gender during a 12-month period. Data was collected from patient records using a questionnaire and analyzed using the SPSS version 20 software. The chi-square test was used to compare the proportions of injuries at a significant level of p &lt; 0.05 and a confidence interval (CI) of 95%. Results A total of 155 participants were recruited in each group. Note that 51.6% were males, and the mean age was 25.46 ± 16.35 years. The 1-year incidence of all injuries was 26.5% in PWE against 16.8% among patients without epilepsy, respectively (p = 0.038; odds ratio = 1.8, 95% CI: 1.03–3.10). Soft tissue injury was higher in PWE (82.9%, p &lt; 0.05) compared to those without epilepsy (50%), whereas patients without epilepsy had more cases of burns compared to PWE (p &lt; 0.05). PWE and having frequent seizures with falls and those on more than one antiseizure medication had an increased risk of injuries (p &lt; 0.05). Conclusion PWE have a double risk of having mild soft tissue injuries attributed to epileptic seizures. The risk is increased in PWE having seizures with falls and those taking more than one antiseizure medication.

Temporal trends, in-hospital outcomes, and risk factors of acute myocardial infarction among patients with epilepsy in the United States: a retrospective national database analysis from 2008 to 2017.

The relationship between epilepsy and risk of acute myocardial infarction (AMI) is not fully understood. Evidence from the Stockholm Heart Study indicates that the risk of AMI is increased in people with epilepsy. This study aims to analyze the temporal trends in prevalence, adverse clinical outcomes, and risk factors of AMI in patients with epilepsy (PWE). Patients aged 18 years or older, diagnosed with epilepsy with or without AMI and hospitalized from January 1, 2008, to December 31, 2017, were identified from the National Inpatient Sample (NIS) database. The Cochran-Armitage trend test and logistic regressions were conducted using SAS 9.4. Odds ratios (ORs) were generated for multiple variables. A total of 8,456,098 inpatients were eligible for our analysis, including 181,826 comorbid with AMI (2.15%). The prevalence of AMI diagnosis in PWE significantly increased from 1,911.7 per 100,000 hospitalizations in 2008 to 2,529.5 per 100,000 hospitalizations in 2017 (Ptrend < 0.001). Inpatient mortality was significantly higher in epilepsy patients with AMI compared to those without AMI (OR = 4.61, 95% CI: 4.54 to 4.69). Factors significantly associated with AMI in PWE included age (≥75 years old vs. 18 ~ 44 years old, OR = 3.54, 95% CI: 3.45 to 3.62), atherosclerosis (OR = 4.44, 95% CI: 4.40 to 4.49), conduction disorders (OR = 2.21, 95% CI: 2.17 to 2.26), cardiomyopathy (OR = 2.11, 95% CI: 2.08 to 2.15), coagulopathy (OR = 1.52, 95% CI: 1.49 to 1.54), dyslipidemia (OR = 1.26, 95% CI: 1.24 to 1.27), peptic ulcer disease (OR = 1.23, 95% CI: 1.13 to 1.33), chronic kidney disease (OR = 1.23, 95% CI: 1.22 to 1.25), smoking (OR = 1.20, 95% CI: 1.18 to 1.21), and weight loss (OR = 1.20, 95% CI: 1.18 to 1.22). The prevalence of AMI in PWE increased during the decade. Mortality rates were high among this population, highlighting the need for comprehensive attention to prophylaxis for risk factors and early diagnosis of AMI in PWE by physicians.

Exercise in patients with epilepsy and neurostimulation devices - physical activity levels, barriers, and beliefs

Exercise improves many comorbidities associated with epilepsy in addition to seizure control. Despite the ILAE consensus statement noting the positive effects of exercise in patients with epilepsy (PWE) and individual assessment of risks pertaining to these activities, many healthcare professionals, including neurologists, are unfamiliar with these guidelines. Neurostimulation is an increasingly prevalent treatment option for refractory epilepsy. To date, no literature exists regarding how PWE treated with neurostimulation devices view and participate in exercise. We surveyed 36 adult PWE treated with neurostimulation (11 VNS, 21 RNS, 3 DBS, 1 VNS+RNS) on their barriers, beliefs, activity levels, and interests in exercise. Forty-three percent of patients reported meeting AHA guidelines for physical activity. Ninety percent of participants noted at least one barrier to exercise with transportation being most common. Fear of embarrassment of a seizure during exercise was reported by 44% with 39% endorsing prior seizure while exercising. Device-specific barriers included fear of device damage or avoidance of specific exercises. There was a statistically significant effect on activity level and prior seizure while exercising. Only 8% of participants reported knowledge of exercise guidelines for PWE. This data provides insight into the views of PWE treated with neurostimulation devices on exercise.

Role of optical coherence tomography as a diagnostic marker for neurodegeneration in epilepsy: a cross-sectional analytical study

BackgroundProgressive neurodegeneration is a common consequence of epilepsy, which has a negative impact on the patient’s quality of life. This study aimed to predict neurodegeneration in patients with epilepsy (PwE) through assessment of the retinal nerve fiber layer (RNFL), ganglion cell complex (GCC) thickness, and central macular thickness (CMT) using optical coherence tomography (OCT).ResultsA cross-sectional study was done on 60 patients with idiopathic epilepsy and 30 healthy volunteers. They were subjected to a full neurological examination, ophthalmological assessment, and OCT for assessment of retinal layers, and cognitive examination using Addenbrooke’s scale. PwE had lower cognitive scores, including memory (13.97 ± 2.52), attention (15.95 ± 1.85), language (24.08 ± 1.71), and fluency (6.10 ± 2.05), compared to controls (20.53 ± 3.5), (17.13 ± 1.53), (24.83 ± 0.99), and (8.87 ± 2.39), respectively. There was a significant thinning in average RNFL thickness (84.27 ± 7.66), inferior RNFL thickness (99.33 ± 10.19), average GCC thickness (83.17 ± 9.76), and superior GCC thickness (84.83 ± 7.27) in the epilepsy group compared to controls (105.70 ± 8.73), (104.93 ± 9.75), (101.50 ± 4.84), and (100.53 ± 4.09), respectively. PwE had significantly higher focal macular volume loss (1.17 ± 1.22) versus (0.11 ± 0.21) and a higher insignificant global macular volume loss (1.88 ± 2.32) versus (1.37 ± 0.65) in controls, respectively. Superior GCC thickness was significantly lower in the uncontrolled patients (82.53 ± 6.23) compared to the controlled patients (87.13 ± 7.60), while CMT was significantly lower in the polytherapy group compared to the monotherapy group. There was a significant positive correlation between the age of epilepsy onset and verbal fluency (r = 0.382, p = 0.003). Epilepsy duration had significant negative correlations with memory (r = − 0.364, p = 0.004), inferior RNFL thickness (r = − 0.324, p = 0.012), perifoveal thickness (r = − 0.353, p = 0.006), and inferior (perifoveal) thickness (r = − 0.365, p = 0.004).ConclusionPwE receiving anti-seizure medications (ASMs) have reduced GCC, RNFL, and CMT and lower cognitive functions compared to controls. OCT may be a useful tool for detection of neurodegeneration in PwE.

The cenobamate KORK study-A prospective monocenter observational study investigating cenobamate as an adjunctive therapy in refractory epilepsy, with comparisons to historical cohorts treated with add-on lacosamide, perampanel, and brivaracetam.

In Europe, cenobamate has been approved for use as an adjunctive therapy in adult patients with epilepsy (PWE) with focal-onset seizures (FOS) who have not responded satisfactorily to treatment with at least two antiseizure medications (ASMs). Pivotal trials and real-world observational studies have demonstrated a high efficacy of cenobamate, even in very difficult-to-treat epilepsies. Our aim was to investigate the efficacy of add-on cenobamate in adult PWE who were prospectively monitored. We compared these results with those previously obtained for add-on lacosamide, perampanel, and brivaracetam therapy. Patients were enrolled from the CENKORK study, which is a prospective, non-interventional, open-label, monocenter cohort study of adult PWE experiencing FOS. The titration of cenobamate was performed according to the guidelines outlined in the summary of product characteristics. The primary outcome measure was the retention rate at 6 months and 1 year. In addition, we assessed seizure-free rates, the proportion of patients achieving at least a 50% seizure reduction, adverse events, and the reasons for treatment discontinuation. These outcome measures were compared with historical controls treated with adjunctive lacosamide, perampanel, or brivaracetam at our center. Between June 2021 and 2022, 172 PWE with ongoing FOS were included. 22 cases were lost to follow-up, leaving 150 cases for the 1-year assessment. The retention rates at 6 months and 1 year were 88.7% and 80%, respectively. Seizure freedom was achieved in 14% of patients at both the 6-month and 1-year marks, while the ≥50% responder rates were 50% and 61%, respectively. The 6-month retention rate was significantly higher in cenobamate than in other ASMs (p < 0.001 for each comparator). Adverse events were significantly more common with perampanel (p < 0.001). Add-on cenobamate proved to be particularly efficacious compared to our experience with other recently introduced ASMs. This observational study was carried out in 172 adult patients with difficult-to-treat epilepsy who were treated with adjunctive cenobamate. After 1 year, the data of 150 patients could be analyzed. Seizure freedom, in the preceding 3 months, was achieved in 14%. The rate of PWE continuing cenobamate was 80%. In our hands, cenobamate showed promising efficacy and tolerability even when compared to other recently introduced antiseizure medications.

Complementary and Alternative Medicine for People with Epilepsy: Opinions of Physicians in Oman.

Several studies have explored the opinions of healthcare workers on the use of complementary and alternative medicine (CAM) in epilepsy treatment. We sought to survey the views of non-neurologist and non-psychiatrist physicians in Oman on the use of CAM for epilepsy. We used convenience sampling to recruit physicians (except neurologists and psychiatrists) from all 11 governorates of Oman. The online questionnaire was open to physicians from 5 January 2022 to 15 February 2023. This study collected anonymous data on their demographics, discipline, work settings, geographical area, and years of practice. Additionally, participants were asked to answer questions about their perception of CAM use and its effectiveness in treating epilepsy. A total of 190 physicians participated, of whom 69.5% were men. Respondents were mostly 36 to 45 years old (51.1%). The majority (52.1%) were general practitioners, 21.1% were internists, 17.9% were pediatricians, and 8.9% were family physicians. Most participants (n = 144; 75.8%) believed that CAM may help treat patients with epilepsy (PWE). The most common therapies that participants considered helpful were meditation (46.0%), prayers (44.7%), yoga (32.6%), and exercise (31.1%). While the evidence supporting the use of CAM for the treatment of epilepsy is scarce, this survey showed that most physicians (non-neurologists and non-psychiatrists), who manage PWE in Oman, believed that some CAM modalities would help treat epilepsy. Well-designed controlled trials are needed to provide reliable evidence on the usefulness of CAM options in PWE.

Risk of COVID-19 infection and seizure exacerbation among patients with epilepsy during the peak of Omicron wave.

Existing data regarding the risk of COVID-19 infection and its effects on seizure control in patients with epilepsy (PWE) are inconclusive. Our research aims to investigate the PWE who are susceptible to COVID-19 and what factors contribute to seizure exacerbation. From Dec 28, 2022 to Feb 19, 2023, a cross-sectional questionnaire survey among adult PWE was conducted. The demographics, epilepsy-related information, COVID-19-related variables, and seizure outcomes after COVID-19 infection were collected. Multivariate logistic analyses were performed to determine the risk factors associated with COVID-19 infection and exacerbated seizures. Of 1557 PWE, 829 (53.2%) were infected with COVID-19 and 136 (16.4%) developed seizure exacerbation after COVID-19 infection. Overweight/obesity (OR 1.372, 95% CI 1.075-1.753,p = 0.011), immunocompromised (OR 3.301, 95% CI 1.093-9.974, p = 0.031), active epilepsy (OR 1.700, 95% CI 1.378-2.097, p < 0.001), and antiseizure medication (ASM) polytherapy (OR 1.314, 95% CI 1.065-1.621, p = 0.011) were associated with COVID-19 infection. Active epilepsy (OR 4.696, 95% CI 2.568-8.586, p < 0.001) and fever-associated seizures (OR 4.298, 95%CI 2.659-6.946, p < 0.001) were associated with seizure exacerbation. PWE with overweight/obesity, immunocompromised, active epilepsy, and ASM polytherapy were at higher risk of COVID-19 infection. Once infected with COVID-19, seizures were exacerbated in PWE with active epilepsy and fever-associated seizures. Patients with epilepsy (PWE) do not appear to be more susceptible to COVID-19 infection than general population. Once infected with COVID-19, 16.4% of PWE had seizure exacerbation. The PWE who have experienced seizures within the past 12 months before infection tend to contract COVID-19 more often, and are more likely to experience seizure exacerbations following COVID-19 infection.

Cenobamate Plasma Levels in Patients with Epilepsy: Correlation with Efficacy and Tolerability?

Objective: Cenobamate is approved by the European Medicine Agency for the treatment of adult patients with epilepsy (PWEs) with ongoing focal-onset seizures despite appropriate treatment with at least two established antiseizure medications. Pivotal trials and post-marketing real-world observational studies suggest high efficacy with unusually high seizure-free rates. The authors sought to investigate the plasma levels of cenobamate under steady-state conditions in seizure-free versus non-responding PWEs, and in PWEs who experienced adverse events versus those who did not. Methods: Blood samples were collected from adult PWEs who were treated with adjunct cenobamate under steady-state conditions. Daily doses, concomitant medications, efficacy, and tolerability were assessed. The plasma cenobamate levels of seizure-free versus non-responding PWEs and between PWEs with and those without clinical adverse events were compared. Results: Samples from 101 PWEs were included. Thirty-six PWEs were seizure-free and 65 were non-responders. In 31 PWEs, adverse events were apparent, whereas in the remaining 70, no tolerability issues were reported. A linear correlation was found between the daily doses (range: 100 mg-400 mg) and the plasma levels (3.8 mg/L-54.6 mg/L). Neither the daily doses nor the plasma levels differed significantly between the investigated subgroups. The main reason for this result was that the individual therapeutic ranges varied widely: seizure freedom and adverse effects were observed alongside low doses and plasma levels in some PWEs. Conversely, there were examples of PWEs who did not respond or who reported no tolerability issues at high doses or plasma levels. Conclusions: To evaluate the individual therapeutic range and to better understand the influence of other drugs in cases where concomitant medications are used, the therapeutic drug monitoring of cenobamate may be useful. A general therapeutic range cannot be defined.

Clinical and sociodemographic characteristics of patients with epilepsy attended at a regional reference psychiatric emergency unit

ObjectiveEpilepsy is one of the most prevalent chronic neurological diseases, presenting a high frequency of psychiatric disorders (PD). This study sought to evaluate the clinical and sociodemographic profile of patients with epilepsy (PWE) attended at a regional reference psychiatric emergency unit. MethodsA retrospective, cross-sectional, and descriptive observational study was conducted utilizing a patient record database of individuals with epilepsy who were attended in a regional reference psychiatric emergency unit between January 2018 and August 2022. ResultsOut of the 31,800 psychiatric emergency visits, 260 (0.8 %) were of patients with epilepsy (ICD-10: G40). The majority were males (63.5 %) with a mean age of 42.11±15.39 years, single marital status (154; 59.25 %) and elementary education (75; 28.9 %). Most of them (203; 78.1 %) presented at least one psychiatric comorbidity at the emergency visit, but 109 (41.9 %) were not receiving any psychiatric follow-up. A total of 106 patients (40.8 %) had experienced at least one past psychiatric hospitalization. ConclusionsThe occurrence of PD is highly prevalent in PWE, and probably with a high frequency of psychiatric emergencies occurring among them. Further studies are needed to assess such patient profile, particularly involving data from psychiatric emergency units.

Anticipatory anxiety of seizures in epilepsy: A common, complex, and underrecognized phenomenon?

The diagnosis of epilepsy is associated with loss of predictability, which invariably results in the fear of when and if future seizures will occur. For a subset of patients with epilepsy (PWE), there may be a pathological persistent fear of seizure occurrence, resulting in limitations to daily activities through avoidant behaviors. Paradoxically, the research of anticipatory anxiety of seizures (AAS; also referred to as seizure phobia) has been practically nonexistent and, not surprisingly, this condition remains underrecognized by clinicians. The available data are derived from three small case series of patients followed in tertiary epilepsy centers. In this study, we review the available data on the reported clinical manifestations of AAS in PWE, and of the potential role of variables associated with it, such as personal and family psychosocial and psychiatric history and epilepsy-related variables. In addition, we review the need for the creation of screening tools to identify patients at risk of AAS and discuss potential treatment strategies, which could be considered as part of the comprehensive management for PWE.

Development and validation of a nonverbal consensus-based semantic memory paradigm in patients with epilepsy.

Brain areas implicated in semantic memory can be damaged in patients with epilepsy (PWE). However, it is challenging to delineate semantic processing deficits from acoustic, linguistic, and other verbal aspects in current neuropsychological assessments. We developed a new Visual-based Semantic Association Task (ViSAT) to evaluate nonverbal semantic processing in PWE. The ViSAT was adapted from similar predecessors (Pyramids & Palm Trees test, PPT; Camels & Cactus Test, CCT) comprised of 100 unique trials using real-life color pictures that avoid demographic, cultural, and other potential confounds. We obtained performance data from 23 PWE participants and 24 control participants (Control), along with crowdsourced normative data from 54 Amazon Mechanical Turk (Mturk) workers. ViSAT reached a consensus >90% in 91.3% of trials compared to 83.6% in PPT and 82.9% in CCT. A deep learning model demonstrated that visual features of the stimulus images (color, shape; i.e., non-semantic) did not influence top answer choices (p = 0.577). The PWE group had lower accuracy than the Control group (p = 0.019). PWE had longer response times than the Control group in general and this was augmented for the semantic processing (trial answer) stage (both p < 0.001). This study demonstrated performance impairments in PWE that may reflect dysfunction of nonverbal semantic memory circuits, such as seizure onset zones overlapping with key semantic regions (e.g., anterior temporal lobe). The ViSAT paradigm avoids confounds, is repeatable/longitudinal, captures behavioral data, and is open-source, thus we propose it as a strong alternative for clinical and research assessment of nonverbal semantic memory.

Effects of stigma on the quality of life in patients with epilepsy

BackgroundThis study was aimed to evaluate the stigma and quality of life (QoL) in adult patients with epilepsy (PWEs) and explore the relationship between stigma and QoL.MethodsTwo hundred and ninety-eight PWEs admitted to the Epilepsy Center of the First Affiliated Hospital of Chongqing Medical University during September 2020 and March 2021 were enrolled in this study. All participants completed self-reported questionnaires including the Stigma Scale for Epilepsy and the Quality of Life in Epilepsy Inventory-31 (QOLIE-31).ResultsA total of 146 (49%) PWEs reported an experience of stigma. The total score of QOLIE-31 and the individual scores of seven subscales (worry about new seizures, emotion, well-being, energy and fatigue, cognitive impairment, medication effect, and social function) were significantly decreased in these patients (P < 0.001). Multivariate stepwise linear regression analysis showed that the annual household income per capita, the number of antiseizure medications and stigma had statistically significant effects on QoL (P < 0.05). Among them, stigma had the most significant negative effect.ConclusionsNearly half of PWEs have experienced stigma. Stigma, lower household income per capita, and polypharmacy treatment are associated with poorer QoL. Stigma has the most obvious negative impact.

Frailty as a comprehensive health measure beyond seizure control in patients with epilepsy: A cross-sectional study.

Due to the high clinical heterogeneity of epilepsy, there is a critical need for novel metrics aimed at capturing its biological and phenotypic complexity. Frailty is increasingly recognized in various medical disciplines as a useful construct to understand differences in susceptibility to adverse outcomes. Here, we develop a frailty index (FI) for patients with epilepsy (PwE) and explore its association with demographic and clinical features. In this cross-sectional study, we consecutively enrolled 153 PwE from an outpatient epilepsy clinic. Participants were assessed for various health deficits to calculate the FI. Associations between FI and demographic/clinical features, antiseizure medications (ASMs), and patient-reported outcomes were analyzed using general linear models and Spearman correlation. The median age at the time of study visit was 47 years (interquartile range = 33-60), and 89 (58.2%) patients were females. Multiple linear regression revealed that the developed 33-item FI showed an independent association with age, female sex, higher body mass index, family history of epilepsy, intellectual disability, and the number of ASMs used. A robust analysis of covariance showed higher FI levels in patients using cytochrome P450 3A4-inducer ASMs. We found a moderate positive correlation between FI and psychological distress, lower quality of life, and physical frailty, measured by the Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy Inventory-10, and handgrip strength, respectively. Finally, a weak association was observed between higher FI scores and an increased number of epileptic falls. This study highlights the significance of frailty as a comprehensive health measure in epilepsy. It suggests that frailty in this specific population is not only a manifestation of aging but is inherently linked to epilepsy and treatment-related factors. Future research is warranted to validate and refine the FI in diverse epilepsy populations and investigate its impact on specific adverse outcomes in longitudinal studies.

Gluten sensitivity based on HLA genotyping in patients with epilepsy in a tertiary hospital in Malaysia

AbstractIntroductionGluten sensitivity (GS) is present in approximately 1% of the Malaysian population (Yap et al., PLoS One, 10, 2015, e0121908). GS is associated with several neurological conditions including epilepsy. Individuals with GS often exhibit a genetic predisposition associated with human leukocyte antigens (HLA) (Cecilio &amp; Bonatto, Arq Bras Cir Dig, 28, 2015, 183). The purpose of this study was to investigate the prevalence of GS based on HLA genotyping in patients with epilepsy (PWE).MethodIn total, 50 PWE and 50 controls were recruited. DNA was extracted from the venous blood samples and genotyped for HLA‐DQ2.2, DQ2.5, DQ7 and DQ 8. In this study, GS was diagnosed if any subject showed positive for one or more of the HLA‐DQ alleles. The type of epilepsy and number of antiseizure medication (ASM) used were recorded.ResultsOnly 2 alleles (HLA‐DQ 2.2 &amp; HLA‐DQ8) were detected among 46 out of 100 subjects. 18 PWE and 19 controls were positive for HLA‐DQ8 (p = 0.836). 9 of the PWE, but no controls were positive for HLA‐DQ 2.2 (p = 0.003). 8 of these 9 PWE who were positive for HLA‐DQ 2.2 were also positive for HLA‐DQ8 (double positive), and these patients required multiple ASM for seizure control (p = 0.006).ConclusionHLA‐DQ2.2 was seen highly prevalent in PWE. The double positives required more than one ASM for seizure control postulating malabsorption of ASM in these individuals. These findings suggest that HLA‐DQ genotyping may be a valuable additional test in PWE especially in those needing more than one ASM. Prescribing gluten‐free diet (GFD) to PWE with GS may potentially be an additional measure to achieve seizure control.