Research indicates that emotions such as anger, guilt, shame, and difficulty tolerating frustration can contribute to harmful behaviors in individuals experiencing both functional/dissociative seizures (FDSs) and post-traumatic stress disorder (PTSD). This study examined the association of guilt and shame with anger through the mediating role of frustration intolerance in patients with simultaneous FDSs and PTSD. The clinical sample of this study included 150 patients with coexisting FDSs and PTSD who were selected using a convenience sampling method in a descriptive study design. The data were collected using the State-Trait Anger Expression Inventory-2nd Edition (STAXI-2), the Guilt and Shame Proneness scale (GASP), and the Frustration Discomfort Scale (FDS). The analysis showed that guilt, shame, and frustration intolerance explained 91.6 % of anger variance among patients with FDSs and PTSD. The findings established that both shame and frustration intolerance are significantly associated with anger. There was no significant direct relationship between guilt and anger. Nevertheless, guilt and shame have significant positive indirect relationships with anger, through the mediating role of frustration intolerance. This study presents a fitted model for the direct and indirect associations between guilt and shame with anger, about the mediating role of frustration intolerance. These results have practical implications for interventions and community-based programs for patients with FDSs and PTSD.
{"title":"The influences of guilt and shame on anger in patients with concurrent psychogenic Non-Epileptic seizures and PTSD: The mediating role of frustration intolerance","authors":"Mahdi Amani , Siamak Khodarahimi , Belgheis Beit-Mashal , Amir Karami , Nasrollah Mazraeh , Mojtaba Rahimian Bougar , Maeda Hesam","doi":"10.1016/j.yebeh.2025.110860","DOIUrl":"10.1016/j.yebeh.2025.110860","url":null,"abstract":"<div><div>Research indicates that emotions such as anger, guilt, shame, and difficulty tolerating frustration can contribute to harmful behaviors in individuals experiencing both functional/dissociative seizures (FDSs) and post-traumatic stress disorder (PTSD). This study examined the association of guilt and shame with anger through the mediating role of frustration intolerance in patients with simultaneous FDSs and PTSD. The clinical sample of this study included 150 patients with coexisting FDSs and PTSD who were selected using a convenience sampling method in a descriptive study design. The data were collected using the State-Trait Anger Expression Inventory-2nd Edition (STAXI-2), the Guilt and Shame Proneness scale (GASP), and the Frustration Discomfort Scale (FDS). The analysis showed that guilt, shame, and frustration intolerance explained 91.6 % of anger variance among patients with FDSs and PTSD. The findings established that both shame and frustration intolerance are significantly associated with anger. There was no significant direct relationship between guilt and anger. Nevertheless, guilt and shame have significant positive indirect relationships with anger, through the mediating role of frustration intolerance. This study presents a fitted model for the direct and indirect associations between guilt and shame with anger, about the mediating role of frustration intolerance. These results have practical implications for interventions and community-based programs for patients with FDSs and PTSD.</div></div>","PeriodicalId":11847,"journal":{"name":"Epilepsy & Behavior","volume":"175 ","pages":"Article 110860"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-11DOI: 10.1016/j.yebeh.2025.110833
Anny Reyes , Jarrod E. Dalton , Bruce P. Hermann , Lisa Ferguson , Imad M. Najm , Robyn M. Busch
Objective
Previous research utilizing neighborhood data has identified a three-factor structure underlying the Area Deprivation Index (ADI), a metric of neighborhood disadvantage. The three factors identified are Financial Strength, Economic Hardship and Inequality, and Educational Attainment. Here, we examine how these distinct dimensions of deprivation are associated with demographic and clinical characteristics, and mood and cognitive outcomes in patients with epilepsy.
Methods
Clinical, demographic, and neuropsychological data were obtained from an IRB-approved clinical registry in a cohort of 1,068 patients (age ≥ 16) with pharmacoresistant epilepsy evaluated for surgery at Cleveland Clinic (2000–2021). Neuropsychological measures assessed general abilities, verbal and nonverbal abilities, attention and working memory, processing speed, memory, language, executive function, and self-reported symptoms of depression and anxiety. Linear regressions were conducted to assess associations between ADI-3 factors and patient outcomes.
Results
Each ADI-3 factor had unique associations with demographic and clinical characteristics, including age, race, education, and epilepsy-related variables, including lower Financial Strength being associated with grater likely of the presence of mesial temporal sclerosis. Lower Financial Strength and Educational Attainment were linked to poorer performance across multiple cognitive domains, including general ability, verbal and nonverbal abilities, and working memory. Financial Strength remained a significant predictor of cognitive performance and greater depressive symptoms even after adjusting for demographic and clinical covariates.
Discussion
These findings support the multidimensional nature of neighborhood deprivation in an epilepsy surgical population and show that ADI-3 factors relate differently to key demographic, clinical, cognitive, and mood outcomes. Financial Strength was strongly and consistently linked to cognitive function and depressive symptoms, highlighting the value of analyzing specific deprivation domains. This approach allows for more precise identification of intervention targets and informs the development of targeted public health strategies to improve outcomes in epilepsy and other neurological conditions.
{"title":"Disentangling deprivation: Differential associations of the area deprivation index- 3 factors with clinical, cognitive, and mood outcomes in epilepsy","authors":"Anny Reyes , Jarrod E. Dalton , Bruce P. Hermann , Lisa Ferguson , Imad M. Najm , Robyn M. Busch","doi":"10.1016/j.yebeh.2025.110833","DOIUrl":"10.1016/j.yebeh.2025.110833","url":null,"abstract":"<div><h3>Objective</h3><div>Previous research utilizing neighborhood data has identified a three-factor structure underlying the Area Deprivation Index (ADI), a metric of neighborhood disadvantage. The three factors identified are Financial Strength, Economic Hardship and Inequality, and Educational Attainment. Here, we examine how these distinct dimensions of deprivation are associated with demographic and clinical characteristics, and mood and cognitive outcomes in patients with epilepsy.</div></div><div><h3>Methods</h3><div>Clinical, demographic, and neuropsychological data were obtained from an IRB-approved clinical registry in a cohort of 1,068 patients (age ≥ 16) with pharmacoresistant epilepsy evaluated for surgery at Cleveland Clinic (2000–2021). Neuropsychological measures assessed general abilities, verbal and nonverbal abilities, attention and working memory, processing speed, memory, language, executive function, and self-reported symptoms of depression and anxiety. Linear regressions were conducted to assess associations between ADI-3 factors and patient outcomes.</div></div><div><h3>Results</h3><div>Each ADI-3 factor had unique associations with demographic and clinical characteristics, including age, race, education, and epilepsy-related variables, including lower Financial Strength being associated with grater likely of the presence of mesial temporal sclerosis. Lower Financial Strength and Educational Attainment were linked to poorer performance across multiple cognitive domains, including general ability, verbal and nonverbal abilities, and working memory. Financial Strength remained a significant predictor of cognitive performance and greater depressive symptoms even after adjusting for demographic and clinical covariates.</div></div><div><h3>Discussion</h3><div>These findings support the multidimensional nature of neighborhood deprivation in an epilepsy surgical population and show that ADI-3 factors relate differently to key demographic, clinical, cognitive, and mood outcomes. Financial Strength was strongly and consistently linked to cognitive function and depressive symptoms, highlighting the value of analyzing specific deprivation domains. This approach allows for more precise identification of intervention targets and informs the development of targeted public health strategies to improve outcomes in epilepsy and other neurological conditions.</div></div>","PeriodicalId":11847,"journal":{"name":"Epilepsy & Behavior","volume":"175 ","pages":"Article 110833"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-10DOI: 10.1016/j.yebeh.2025.110854
George Vasconcelos Calheiros de Oliveira Costa , Ana Leticia Fornari Caprara , Jamir Pitton Rissardo , Alba Letícia Peixoto Medeiros , Matheus Bernardon Morillos , Carolina Machado Torres , Marino Muxfeldt Bianchin
Background
Epileptic prodromes have historically received limited attention due to their subjective nature and limited localizing value. However, they hold potential for seizure prediction, which could significantly influence epilepsy management.
Objective
This cross-sectional research aimed to examine whether the presence and characteristics of epileptic prodromes relate to seizure reactivity, Health Locus of Control (HLC), anxiety, and depression in individuals with drug-resistant epilepsy (DRE).
Methods
A cross-sectional study of DRE patients which evaluated clinical variables, prodromal symptoms, reactivity to prodromes, HLC, and neuropsychiatric symptoms.
Results
Seventy-four patients (22 men, 29.7 %; 52 women, 70.3 %) were included; mean age was 42.3 ± 14.6 years. Mean age at epilepsy onset was 14.9 ± 12.3 years, and mean disease duration was 27.5 ± 16.0 years. Significant negative correlations were observed between internal HLC and anxiety (rho = -0.347, p = 0.002) and depression (rho = -0.488, p < 0.001). Conversely, chance HLC correlated positively with disease duration (rho = 0.319, p = 0.006) and depression (rho = 0.367, p = 0.001). Patients reporting three or more prodromal symptom types had sixfold increased odds of seizure reactivity (OR = 6.25, 95 % CI = 2.11–18.46, p = 0.001).
Conclusions
The belief that one’s own actions, behaviors, and internal factors are responsible for their health outcomes appears protective against anxiety and depression in individuals with DRE. Longer epilepsy duration and higher depression levels are associated with a belief that health outcomes are governed by luck or fate. Reporting prodromes significantly increases the likelihood of seizure reactivity, highlighting their potential role in seizure forecasting.
历史上，由于其主观性和局限性，癫痫前驱症状受到的关注有限。然而，它们具有癫痫发作预测的潜力，这可能会显著影响癫痫的管理。目的本横断面研究旨在探讨癫痫前驱症状的存在及其特征是否与耐药癫痫（DRE）患者发作反应性、健康控制点（HLC）、焦虑和抑郁有关。方法对DRE患者进行横断面研究，评估临床变量、前驱症状、对前驱症状的反应性、hcc和神经精神症状。结果共纳入74例患者，其中男性22例，占29.7%；女性52例，占70.3%；平均年龄42.3±14.6岁。平均发病年龄14.9±12.3岁，平均病程27.5±16.0岁。内部HLC与焦虑（rho = -0.347, p = 0.002）和抑郁（rho = -0.488, p < 0.001）呈显著负相关。相反，发病率与病程（rho = 0.319, p = 0.006）和抑郁（rho = 0.367, p = 0.001）呈正相关。报告三种或三种以上前驱症状类型的患者发作反应性的几率增加了6倍（or = 6.25, 95% CI = 2.11-18.46, p = 0.001）。结论：相信自己的行动、行为和内在因素对他们的健康结果负责，似乎对DRE患者的焦虑和抑郁有保护作用。更长的癫痫持续时间和更高的抑郁程度与一种信念有关，即健康结果由运气或命运决定。报告前驱症状可显著增加癫痫发作反应性的可能性，突出其在癫痫发作预测中的潜在作用。
{"title":"Evaluating prodromal symptoms and health locus of control as predictors of seizure reactivity and neuropsychiatric outcomes in drug-resistant epilepsy: a cross-sectional study","authors":"George Vasconcelos Calheiros de Oliveira Costa , Ana Leticia Fornari Caprara , Jamir Pitton Rissardo , Alba Letícia Peixoto Medeiros , Matheus Bernardon Morillos , Carolina Machado Torres , Marino Muxfeldt Bianchin","doi":"10.1016/j.yebeh.2025.110854","DOIUrl":"10.1016/j.yebeh.2025.110854","url":null,"abstract":"<div><h3>Background</h3><div>Epileptic prodromes have historically received limited attention due to their subjective nature and limited localizing value. However, they hold potential for seizure prediction, which could significantly influence epilepsy management.</div></div><div><h3>Objective</h3><div>This cross-sectional research aimed to examine whether the presence and characteristics of epileptic prodromes relate to seizure reactivity, Health Locus of Control (HLC), anxiety, and depression in individuals with drug-resistant epilepsy (DRE).</div></div><div><h3>Methods</h3><div>A cross-sectional study of DRE patients which evaluated clinical variables, prodromal symptoms, reactivity to prodromes, HLC, and neuropsychiatric symptoms.</div></div><div><h3>Results</h3><div>Seventy-four patients (22 men, 29.7 %; 52 women, 70.3 %) were included; mean age was 42.3 ± 14.6 years. Mean age at epilepsy onset was 14.9 ± 12.3 years, and mean disease duration was 27.5 ± 16.0 years. Significant negative correlations were observed between internal HLC and anxiety (rho = -0.347, <em>p</em> = 0.002) and depression (rho = -0.488, <em>p</em> < 0.001). Conversely, chance HLC correlated positively with disease duration (rho = 0.319, p = 0.006) and depression (rho = 0.367, <em>p</em> = 0.001). Patients reporting three or more prodromal symptom types had sixfold increased odds of seizure reactivity (OR = 6.25, 95 % CI = 2.11–18.46, <em>p</em> = 0.001).</div></div><div><h3>Conclusions</h3><div>The belief that one’s own actions, behaviors, and internal factors are responsible for their health outcomes appears protective against anxiety and depression in individuals with DRE. Longer epilepsy duration and higher depression levels are associated with a belief that health outcomes are governed by luck or fate. Reporting prodromes significantly increases the likelihood of seizure reactivity, highlighting their potential role in seizure forecasting.</div></div>","PeriodicalId":11847,"journal":{"name":"Epilepsy & Behavior","volume":"175 ","pages":"Article 110854"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-02DOI: 10.1016/j.yebeh.2025.110841
Ruken Simsekoglu , Emre Akbas , Serra Sandor , Hasan Demirci , Temel Tombul
Objective
To investigate social cognitive functions, specifically theory of mind (ToM) and alexithymia, in patients with cryptogenic frontal lobe epilepsy (FLE) without detectable structural brain lesions, and examine their associations with clinical, and demographic characteristics.
Methods
A total of 14 patients with cryptogenic FLE, and 30 age-, sex-, and education-matched healthy controls (HCs) were included. The participants were aged 18 years or older. The Reading the Mind in the Eyes Test (RMET) was used to assess ToM, and the Toronto Alexithymia Scale-20 (TAS-20) was used to evaluate alexithymia. Depression symptoms were controlled using the Beck Depression Inventory (BDI).
Results
Patients with cryptogenic FLE showed significantly lower RMET scores, indicating poorer affective ToM, and higher TAS-20 total scores, indicating greater alexithymia, compared with the HCs. These differences remained significant after controlling for BDI. No significant associations were found between ToM or alexithymia scores, and clinical parameters such as age at onset, duration of epilepsy, or seizure frequency. Within the cryptogenic FLE group, male patients showed a trend toward poorer social cognitive performance compared with females, although this difference did not reach statistical significance.
Conclusion
Cryptogenic FLE is associated with impairments in ToM, and elevated alexithymia, independent of depressive symptoms and clinical epilepsy variables. These findings indicate that social cognitive dysfunctions may occur even in the absence of structural brain abnormalities and underscore the role of frontal networks in emotional awareness and affective mentalizing.
目的探讨隐源性额叶癫痫（FLE）患者的社会认知功能，特别是心理理论（ToM）和述情障碍，并探讨其与临床和人口统计学特征的关系。方法共纳入14例隐源性FLE患者和30例年龄、性别和教育程度相匹配的健康对照（hc）。参与者年龄在18岁以上。采用RMET （Reading The Mind in The Eyes Test）评估ToM，采用多伦多述情量表-20 （TAS-20）评估述情。采用贝克抑郁量表（BDI）控制抑郁症状。结果与hc患者相比，隐源性FLE患者的RMET评分明显较低，表明情感ToM较差；TAS-20总分较高，表明述情障碍较重。在控制BDI后，这些差异仍然显著。ToM或述情障碍评分与发病年龄、癫痫持续时间或发作频率等临床参数之间未发现显著关联。在隐源性FLE组中，男性患者的社会认知表现较女性患者差，但差异无统计学意义。结论隐源性FLE与ToM损伤和述情障碍升高有关，独立于抑郁症状和临床癫痫变量。这些发现表明，即使在没有大脑结构异常的情况下，社会认知功能障碍也可能发生，并强调了额叶网络在情绪意识和情感心智化中的作用。
{"title":"Theory of mind and alexithymia in patients with cryptogenic frontal lobe epilepsy","authors":"Ruken Simsekoglu , Emre Akbas , Serra Sandor , Hasan Demirci , Temel Tombul","doi":"10.1016/j.yebeh.2025.110841","DOIUrl":"10.1016/j.yebeh.2025.110841","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate social cognitive functions, specifically theory of mind (ToM) and alexithymia, in patients with cryptogenic frontal lobe epilepsy (FLE) without detectable structural brain lesions, and examine their associations with clinical, and demographic characteristics.</div></div><div><h3>Methods</h3><div>A total of 14 patients with cryptogenic FLE, and 30 age-, sex-, and education-matched healthy controls (HCs) were included. The participants were aged 18 years or older. The<!--> <!-->Reading the Mind in the Eyes Test (RMET)<!--> <!-->was used to assess ToM, and the<!--> <!-->Toronto Alexithymia Scale-20 (TAS-20)<!--> <!-->was used to evaluate alexithymia. Depression symptoms were controlled using the Beck Depression Inventory (BDI).</div></div><div><h3>Results</h3><div>Patients with cryptogenic FLE showed significantly lower RMET scores, indicating poorer affective ToM, and higher TAS-20 total scores, indicating greater alexithymia, compared with the HCs. These differences remained significant after controlling for BDI. No significant associations were found between ToM or alexithymia scores, and clinical parameters such as age at onset, duration of epilepsy, or seizure frequency. Within the cryptogenic FLE group, male patients showed a trend toward poorer social cognitive performance compared with females, although this difference did not reach statistical significance.</div></div><div><h3>Conclusion</h3><div>Cryptogenic FLE is associated with impairments in ToM, and elevated alexithymia, independent of depressive symptoms and clinical epilepsy variables. These findings indicate that social cognitive dysfunctions may occur even in the absence of structural brain abnormalities and underscore the role of frontal networks in emotional awareness and affective mentalizing.</div></div>","PeriodicalId":11847,"journal":{"name":"Epilepsy & Behavior","volume":"175 ","pages":"Article 110841"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145651763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-06DOI: 10.1016/j.yebeh.2025.110853
Kathleen L. Cui , Robert Moss , Vikram R. Rao , Sharon Chiang
Objective
Epileptic seizures (ES) and functional seizures (FS) commonly coexist. People with both conditions (ES + FS) report different contributing factors to quality of life (QOL) compared to people with ES only. However, a distinct core outcome set (COS) for measuring QOL among people with ES + FS does not exist.
Methods
We analyzed cross-sectional data from an existing Delphi consensus study that defined a QOL COS for adults with self-reported epilepsy with or without comorbid FS. Participants assigned importance rankings via a 9-point Likert scale to 248 QOL outcomes. A potential COS inclusion list was identified via established consensus thresholds. Differences in QOL priorities between those with and without comorbid FS were evaluated by Wilcoxon rank-sum tests.
Results
Of 291 adults with epilepsy, 269 had ES and 22 had ES + FS. People with ES + FS assigned critical importance to more QOL outcomes across a wider range of domains, particularly in functional, psychiatric, and healthcare utilization areas. 38 QOL outcomes were rated as critically important for potential inclusion in a COS for people with ES + FS. There were differences in QOL priorities between groups, with people with ES + FS assigning higher importance to having questions on “having thoughts of suicide” and items related to high-acuity, frequent, and prolonged encounters with the healthcare system.
Significance
Measuring QOL in people with ES + FS, who assigned greater importance to suicidal ideation and healthcare utilization items, requires an overlapping but distinct COS when compared to people with ES.
{"title":"Unique quality of life priorities for people with epilepsy and comorbid functional seizures","authors":"Kathleen L. Cui , Robert Moss , Vikram R. Rao , Sharon Chiang","doi":"10.1016/j.yebeh.2025.110853","DOIUrl":"10.1016/j.yebeh.2025.110853","url":null,"abstract":"<div><h3>Objective</h3><div>Epileptic seizures (ES) and functional seizures (FS) commonly coexist. People with both conditions (ES + FS) report different contributing factors to quality of life (QOL) compared to people with ES only. However, a distinct core outcome set (COS) for measuring QOL among people with ES + FS does not exist.</div></div><div><h3>Methods</h3><div>We analyzed cross-sectional data from an existing Delphi consensus study that defined a QOL COS for adults with self-reported epilepsy with or without comorbid FS. Participants assigned importance rankings via a 9-point Likert scale to 248 QOL outcomes. A potential COS inclusion list was identified via established consensus thresholds. Differences in QOL priorities between those with and without comorbid FS were evaluated by Wilcoxon rank-sum tests.</div></div><div><h3>Results</h3><div>Of 291 adults with epilepsy, 269 had ES and 22 had ES + FS. People with ES + FS assigned critical importance to more QOL outcomes across a wider range of domains, particularly in functional, psychiatric, and healthcare utilization areas. 38 QOL outcomes were rated as critically important for potential inclusion in a COS for people with ES + FS. There were differences in QOL priorities between groups, with people with ES + FS assigning higher importance to having questions on “having thoughts of suicide” and items related to high-acuity, frequent, and prolonged encounters with the healthcare system.</div></div><div><h3>Significance</h3><div>Measuring QOL in people with ES + FS, who assigned greater importance to suicidal ideation and healthcare utilization items, requires an overlapping but distinct COS when compared to people with ES.</div></div>","PeriodicalId":11847,"journal":{"name":"Epilepsy & Behavior","volume":"175 ","pages":"Article 110853"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To assess the psychiatric side effects of cenobamate (CNB) in adults with focal-onset drug-resistant epilepsy, evaluate its impact on pre-existing psychiatric comorbidities, and identify potential risk factors contributing to psychiatric symptom development.
Methods
This single-center, retrospective observational study included 60 patients who received CNB treatment for a minimum of six months. Clinical data, psychiatric history, and treatment outcomes were obtained through patient interviews and medical records. Psychiatric comorbidities were evaluated by experienced clinicians. Seizure outcomes and psychiatric effects were analyzed descriptively.
Results
Cenobamate demonstrated high efficacy, with 12 % of patients achieving complete seizure freedom and 57 % experiencing a ≥50 % reduction in seizure frequency. No cases of new-onset psychiatric adverse effects were observed. Among the 22 patients presenting with psychiatric or behavioural symptoms at CNB initiation, 68 % showed no change at follow-up, 9 % experienced an improvement in their pre-existing psychiatric condition, and 23 % showed worsening of symptoms. All five patients with worsening symptoms had intellectual disabilities, exhibited irritability or aggressive behavior at baseline, and responded positively to seizure treatment. In contrast, none of the 13 patients with psychiatric or behavioural symptoms and normal cognitive profiles experienced any psychiatric deterioration.
Conclusion
Cenobamate did not induce new psychiatric side effects and was well tolerated in patients with pre-existing psychiatric conditions and normal intellectual functioning. However, in individuals with intellectual disabilities and baseline psychiatric comorbidities, CNB may exacerbate irritability through multifactorial mechanisms.
{"title":"Psychiatric effects of cenobamate in adults with epilepsy: A retrospective study","authors":"Monica Ferlisi , Carlotta Trespidi , Cecilia Zivelonghi , Bruno Bonetti , Tiziano Zanoni","doi":"10.1016/j.yebeh.2025.110838","DOIUrl":"10.1016/j.yebeh.2025.110838","url":null,"abstract":"<div><h3>Aim</h3><div>To assess the psychiatric side effects of cenobamate (CNB) in adults with focal-onset drug-resistant epilepsy, evaluate its impact on pre-existing psychiatric comorbidities, and identify potential risk factors contributing to psychiatric symptom development.</div></div><div><h3>Methods</h3><div>This single-center, retrospective observational study included 60 patients who received CNB treatment for a minimum of six months. Clinical data, psychiatric history, and treatment outcomes were obtained through patient interviews and medical records. Psychiatric comorbidities were evaluated by experienced clinicians. Seizure outcomes and psychiatric effects were analyzed descriptively.</div></div><div><h3>Results</h3><div>Cenobamate demonstrated high efficacy, with 12 % of patients achieving complete seizure freedom and 57 % experiencing a ≥50 % reduction in seizure frequency. No cases of new-onset psychiatric adverse effects were observed. Among the 22 patients presenting with psychiatric or behavioural symptoms at CNB initiation, 68 % showed no change at follow-up, 9 % experienced an improvement in their pre-existing psychiatric condition, and 23 % showed worsening of symptoms. All five patients with worsening symptoms had intellectual disabilities, exhibited irritability or aggressive behavior at baseline, and responded positively to seizure treatment. In contrast, none of the 13 patients with psychiatric or behavioural symptoms and normal cognitive profiles experienced any psychiatric deterioration.</div></div><div><h3>Conclusion</h3><div>Cenobamate did not induce new psychiatric side effects and was well tolerated in patients with pre-existing psychiatric conditions and normal intellectual functioning. However, in individuals with intellectual disabilities and baseline psychiatric comorbidities, CNB may exacerbate irritability through multifactorial mechanisms.</div></div>","PeriodicalId":11847,"journal":{"name":"Epilepsy & Behavior","volume":"175 ","pages":"Article 110838"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145651766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-11DOI: 10.1016/j.yebeh.2025.110851
William E. Rosenfeld , Louis Ferrari
Objective
To examine initial doses of cenobamate that were associated with seizure freedom (100% seizure reduction) in a subset of patients from a large, open-label, phase 3 safety study.
Methods
We reviewed available focal seizure efficacy data for patients (N = 240) from 10 eligible US study sites. Among patients achieving seizure freedom for ≥12 months (≥350 consecutive days) and ≥24 months (≥700 consecutive days) at last clinic visit, or at any time during the analysis, the doses of cenobamate at the start of their seizure-free interval were examined. We also examined cenobamate doses for ≥12-month and ≥24-month seizure freedom stratified by baseline seizure frequency (< 3 vs ≥3 seizures/28 days).
Results
Of 62 patients with ≥12-month seizure freedom at their last visit, 24.2 % (15/62) of patients started their seizure-free interval at cenobamate doses ≤50 mg/day, 4.8 % (3/62) at 100 mg/day, 14.5 % (9/62) at 150 mg/day, and 12.9 % (8/62) at 200 mg/day. Of 33 patients who were seizure-free for ≥24 months at their last study visit, 45.5 % (15/33) started their seizure-free interval on cenobamate doses ≤ 50 mg/day, 3.0 % (1/33) at 100 mg/day, 15.2 % (5/33) at 150 mg/day, and 12.1 % (4/33) at 200 mg/day.
Conclusion
Of 62/240 patients achieving 12-month seizure freedom at last visit, 35/62 started their seizure-free interval at cenobamate doses ≤200 mg/day (24-month: 25/33). Attaining seizure freedom at a lower dose may be predictive of remaining seizure-free for a longer period. Further prospective research is needed to better define cenobamate’s efficacy at lower doses.
{"title":"Wide range of cenobamate doses associated with initial seizure freedom in patients with uncontrolled focal seizures: Post-hoc analysis of a phase 3, multicenter, open-label study","authors":"William E. Rosenfeld , Louis Ferrari","doi":"10.1016/j.yebeh.2025.110851","DOIUrl":"10.1016/j.yebeh.2025.110851","url":null,"abstract":"<div><h3>Objective</h3><div>To examine initial doses of cenobamate that were associated with seizure freedom (100% seizure reduction) in a subset of patients from a large, open-label, phase 3 safety study.</div></div><div><h3>Methods</h3><div>We reviewed available focal seizure efficacy data for patients (<em>N</em> = 240) from 10 eligible US study sites. Among patients achieving seizure freedom for ≥12 months (≥350 consecutive days) and ≥24 months (≥700 consecutive days) at last clinic visit, or at any time during the analysis, the doses of cenobamate at the start of their seizure-free interval were examined. We also examined cenobamate doses for ≥12-month and ≥24-month seizure freedom stratified by baseline seizure frequency (< 3 vs ≥3 seizures/28 days).</div></div><div><h3>Results</h3><div>Of 62 patients with ≥12-month seizure freedom at their last visit, 24.2 % (15/62) of patients started their seizure-free interval at cenobamate doses ≤50 mg/day, 4.8 % (3/62) at 100 mg/day, 14.5 % (9/62) at 150 mg/day, and 12.9 % (8/62) at 200 mg/day. Of 33 patients who were seizure-free for ≥24 months at their last study visit, 45.5 % (15/33) started their seizure-free interval on cenobamate doses ≤ 50 mg/day, 3.0 % (1/33) at 100 mg/day, 15.2 % (5/33) at 150 mg/day, and 12.1 % (4/33) at 200 mg/day.</div></div><div><h3>Conclusion</h3><div>Of 62/240 patients achieving 12-month seizure freedom at last visit, 35/62 started their seizure-free interval at cenobamate doses ≤200 mg/day (24-month: 25/33). Attaining seizure freedom at a lower dose may be predictive of remaining seizure-free for a longer period. Further prospective research is needed to better define cenobamate’s efficacy at lower doses.</div></div>","PeriodicalId":11847,"journal":{"name":"Epilepsy & Behavior","volume":"175 ","pages":"Article 110851"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-03DOI: 10.1016/j.yebeh.2025.110850
Lars Kullman
This review analyzes 155 papers published between 1966 and 2025 examining epilepsy in 108 famous persons (see Supplementary Material for complete list), using the PubMed “famous persons” MeSH term combined with epilepsy-related search terms. Vincent van Gogh (37 papers, 23.9 %) and Fyodor Dostoevsky (34 papers, 21.9 %) dominated the literature, together accounting for 45.8 % of all publications. Writers and artists received the most scholarly attention, with 72.3 % of papers published after 2000. Most papers discussed epilepsy generally without specifying type, while temporal lobe epilepsy was the most specified subtype. Notable biases were identified: 89.8 % male subjects and 44.0 % from 19th-20th centuries. The extreme concentration on Van Gogh and Dostoevsky, combined with significant gender and temporal biases, raises questions about publication bias and the perpetuation of medical mythology. While retrospective diagnosis remains methodologically challenging, this literature provides valuable insights into changing medical paradigms and societal attitudes toward epilepsy.
本综述使用PubMed“名人”MeSH术语结合癫痫相关搜索词，分析了1966年至2025年间发表的155篇论文，研究了108位名人的癫痫（完整列表见补充材料）。Vincent van Gogh（37篇，23.9%）和Fyodor Dostoevsky（34篇，21.9%）占据主导地位，共占总发表量的45.8%。作家和艺术家受到的学术关注最多，2000年以后发表的论文占72.3%。大多数文献对癫痫的讨论一般不明确类型，而颞叶癫痫是最明确的亚型。发现了显著的偏差：89.8%的受试者为男性，44.0%的受试者来自19 -20世纪。对梵高（Van Gogh）和陀思妥耶夫斯基（Dostoevsky）的极度关注，加上明显的性别和时间偏见，引发了有关出版偏见和医学神话永久化的问题。虽然回顾性诊断在方法上仍然具有挑战性，但这些文献为改变医学范式和社会对癫痫的态度提供了有价值的见解。
{"title":"Famous persons with epilepsy – Trends and patterns in the medical literature","authors":"Lars Kullman","doi":"10.1016/j.yebeh.2025.110850","DOIUrl":"10.1016/j.yebeh.2025.110850","url":null,"abstract":"<div><div>This review analyzes 155 papers published between 1966 and 2025 examining epilepsy in 108 famous persons (see <span><span>Supplementary Material</span></span> for complete list), using the PubMed “famous persons” MeSH term combined with epilepsy-related search terms. Vincent van Gogh (37 papers, 23.9 %) and Fyodor Dostoevsky (34 papers, 21.9 %) dominated the literature, together accounting for 45.8 % of all publications. Writers and artists received the most scholarly attention, with 72.3 % of papers published after 2000. Most papers discussed epilepsy generally without specifying type, while temporal lobe epilepsy was the most specified subtype. Notable biases were identified: 89.8 % male subjects and 44.0 % from 19th-20th centuries. The extreme concentration on Van Gogh and Dostoevsky, combined with significant gender and temporal biases, raises questions about publication bias and the perpetuation of medical mythology. While retrospective diagnosis remains methodologically challenging, this literature provides valuable insights into changing medical paradigms and societal attitudes toward epilepsy.</div></div>","PeriodicalId":11847,"journal":{"name":"Epilepsy & Behavior","volume":"175 ","pages":"Article 110850"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-11DOI: 10.1016/j.yebeh.2025.110802
Xinyi Zhou , Jing Ning , Yingfan Wang, Minghao Li, Jing Lu, Yinjie Zhu, Peilin Jiang, Ke Hu, Wenkang Li, Xiaoshan Wang
Objective
This study was aimed to explore the mechanisms of seizure initiation, propagation, and termination in childhood absence epilepsy (CAE) by analyzing dynamic whole-brain network changes.
Methods
We recruited 37 unmedicated children with CAE and recorded magnetoencephalographic (MEG) data from 65 seizures and interictal periods. The seizure course was time-segmented, and a dynamic frequency analysis was conducted. Functional connectivity (FC) was assessed using corrected amplitude envelope correlation (AEC-c), and total node strengths were calculated based on AEC-c values.
Results
Total node strength exhibited distinct temporal and frequency-specific changes. Preictally, it increased in all frequency bands except alpha (P < 0.05). Ictally, it decreased below interictal levels in the delta/theta bands but increased in all others (P < 0.05). Postictally, it remained altered. Regarding FC, brain network reorganization began as early as the preictal phase. At seizure termination, beta synchronization declined first, while delta and gamma2 showed a transient peak.
Conclusion
This study characterized the dynamic reconfiguration of whole-brain functional networks across seizure phases in CAE, highlighting time- and frequency-specific changes.
Significance
By framing CAE as a network disorder, this study emphasized the importance of frequency-specific analyses in epilepsy research and provide insights to guide future frequency-targeted diagnostics and therapies.
{"title":"The whole-brain dynamic neuromagnetic network characteristics in childhood absence epilepsy: A multi-frequency magnetoencephalography study","authors":"Xinyi Zhou , Jing Ning , Yingfan Wang, Minghao Li, Jing Lu, Yinjie Zhu, Peilin Jiang, Ke Hu, Wenkang Li, Xiaoshan Wang","doi":"10.1016/j.yebeh.2025.110802","DOIUrl":"10.1016/j.yebeh.2025.110802","url":null,"abstract":"<div><h3>Objective</h3><div>This study was aimed to explore the mechanisms of seizure initiation, propagation, and termination in childhood absence epilepsy (CAE) by analyzing dynamic whole-brain network changes.</div></div><div><h3>Methods</h3><div>We recruited 37 unmedicated children with CAE and recorded magnetoencephalographic (MEG) data from 65 seizures and interictal periods. The seizure course was time-segmented, and a dynamic frequency analysis was conducted. Functional connectivity (FC) was assessed using corrected amplitude envelope correlation (AEC-c), and total node strengths were calculated based on AEC-c values.</div></div><div><h3>Results</h3><div>Total node strength exhibited distinct temporal and frequency-specific changes. Preictally, it increased in all frequency bands except alpha (P < 0.05). Ictally, it decreased below interictal levels in the delta/theta bands but increased in all others (P < 0.05). Postictally, it remained altered. Regarding FC, brain network reorganization began as early as the preictal phase. At seizure termination, beta synchronization declined first, while delta and gamma2 showed a transient peak.</div></div><div><h3>Conclusion</h3><div>This study characterized the dynamic reconfiguration of whole-brain functional networks across seizure phases in CAE, highlighting time- and frequency-specific changes.</div></div><div><h3>Significance</h3><div>By framing CAE as a network disorder, this study emphasized the importance of frequency-specific analyses in epilepsy research and provide insights to guide future frequency-targeted diagnostics and therapies.</div></div>","PeriodicalId":11847,"journal":{"name":"Epilepsy & Behavior","volume":"175 ","pages":"Article 110802"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-11DOI: 10.1016/j.yebeh.2025.110826
Li Qin , Bei Chen , Ling Xiao , Haoyue Zhu , Manliu Hou , Xiaoyan Long , Weiting Tang , Xiaobo Zhang , Ming Qv , Yongxiang Tang , Zhimin Zhang , Shuo Hu , Li Feng
Background and objectives
Current therapeutic interventions towards cognitive deficits in temporal lobe epilepsy (TLE) remain suboptimal due to incomplete elucidation of the underlying pathophysiological mechanisms. Emerging evidence implicates synapse loss as a critical neuropathological substrate associated with cognitive dysfunction. Given that synapse constitute the fundamental structural units of neural circuit and established disruption of cognitive networks in epilepsy, this study innovatively explores epileptic cognitive network alteration from synaptic viewpoint.
Methods
Utilizing [18F]SynVesT-1 positron emission tomography (PET) for in-vivo synaptic density quantification and Kullback-Leibler Divergence Similarity Estimation (KLSE) depicting for individual-level network characterization, we identified synaptic connectome alteration in TLE patients. The relationship between abnormal synaptic connectivity and cognitive assessment scores was evaluated by Spearman correlation analysis.
Results
We observed significant global reduction in edge connectivity and decreased weighted connectivity strength in TLE, which correlates with impaired neuropsychological performance in both intelligence and memory domains respectively. Hypoconnectivity in the frontal lobe and superior temporal gyrus correlated with poorer linguistic intelligence quotient (IQ). The caudate nucleus emerged as a critical hub, with its eigenvector centrality showing positive associations with both spatial skills and full-scale intelligence quotient (FSIQ). Hippocampal-posterior cortical circuitry involving the interaction between the hippocampus and the lingual gyrus, angular gyrus, calcarine fissure, mediated the variance in memory quotient (MQ).
Conclusion
These findings suggest that synaptic connectivity attenuation may serve as a novel biomarker for cognitive deficits in temporal lobe epilepsy, providing an innovative perspective for targeted clinical interventions.
{"title":"Novel insights into cognitive network alterations in temporal lobe epilepsy: A [18F]SynVesT-1 PET study","authors":"Li Qin , Bei Chen , Ling Xiao , Haoyue Zhu , Manliu Hou , Xiaoyan Long , Weiting Tang , Xiaobo Zhang , Ming Qv , Yongxiang Tang , Zhimin Zhang , Shuo Hu , Li Feng","doi":"10.1016/j.yebeh.2025.110826","DOIUrl":"10.1016/j.yebeh.2025.110826","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Current therapeutic interventions towards cognitive deficits in temporal lobe epilepsy (TLE) remain suboptimal due to incomplete elucidation of the underlying pathophysiological mechanisms. Emerging evidence implicates synapse loss as a critical neuropathological substrate associated with cognitive dysfunction. Given that synapse constitute the fundamental structural units of neural circuit and established disruption of cognitive networks in epilepsy, this study innovatively explores epileptic cognitive network alteration from synaptic viewpoint.</div></div><div><h3>Methods</h3><div>Utilizing [<sup>18</sup>F]SynVesT-1 positron emission tomography (PET) for in-vivo synaptic density quantification and Kullback-Leibler Divergence Similarity Estimation (KLSE) depicting for individual-level network characterization, we identified synaptic connectome alteration in TLE patients. The relationship between abnormal synaptic connectivity and cognitive assessment scores was evaluated by Spearman correlation analysis.</div></div><div><h3>Results</h3><div>We observed significant global reduction in edge connectivity and decreased weighted connectivity strength in TLE, which correlates with impaired neuropsychological performance in both intelligence and memory domains respectively. Hypoconnectivity in the frontal lobe and superior temporal gyrus correlated with poorer linguistic intelligence quotient (IQ). The caudate nucleus emerged as a critical hub, with its eigenvector centrality showing positive associations with both spatial skills and full-scale intelligence quotient (FSIQ). Hippocampal-posterior cortical circuitry involving the interaction between the hippocampus and the lingual gyrus, angular gyrus, calcarine fissure, mediated the variance in memory quotient (MQ).</div></div><div><h3>Conclusion</h3><div>These findings suggest that synaptic connectivity attenuation may serve as a novel biomarker for cognitive deficits in temporal lobe epilepsy, providing an innovative perspective for targeted clinical interventions.</div></div>","PeriodicalId":11847,"journal":{"name":"Epilepsy & Behavior","volume":"175 ","pages":"Article 110826"},"PeriodicalIF":2.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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