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Objective: We investigated the association between the glucocorticoid receptor (GR) gene, also known as the nuclear receptor subfamily 3, group C, member 1 (NR3C1), rs41423247 polymorphism, and functional seizures (psychogenic nonepileptic seizures/attacks) in a case–control study. We hypothesized that the tested polymorphism has significant associations with functional seizures (psychogenic nonepileptic seizures/attacks) independent from comorbid depression. Methods: Seventy patients with functional seizures (psychogenic nonepileptic seizures/attacks), 70 with major depressive disorder (MDD), and 70 healthy controls (HCs) were studied. Their DNAs were analyzed for NR3C1 rs41423247 polymorphism. Results: Genotype and allele frequencies of rs41423247 were different between the three groups. G allele carriers were more frequent in patients with functional seizures (psychogenic nonepileptic seizures/attacks) and those with MDD compared to HCs (p = 0.0001). However no significant difference was observed with respect to allele distributions between functional seizures (psychogenic nonepileptic seizures/attacks) and MDD groups (p = 0.391). CC genotype was less often associated with functional seizures (psychogenic nonepileptic seizures/attacks) versus HC: Codominant model; p = 0.001, OR = 0.11, 95% CI = 0.05–0.24, and −2loglilkelihood = 231.7. In comparison between functional seizures (psychogenic nonepileptic seizures/attacks) group and other (MDD + HC) groups, we observed a significant association between CG genotype and functional seizures (psychogenic nonepileptic seizures/attacks) (Codominant model; p = 0.001, OR = 5.63, 95% CI = 2.60–12.40 and −2loglikelihood = 245.99). Significance: Patients with functional seizures (psychogenic nonepileptic seizures/attacks) and those with MDD were significantly more often G allele carriers in rs41423247 compared with HCs. We observed a significant association between CG genotype and functional seizures (psychogenic nonepileptic seizures/attacks). However, we could not exclude the possibility of confounding effects of depression. Future genetic studies of patients with functional seizures (psychogenic nonepileptic seizures/attacks) should include a comparison group with depression in addition to a comparison group of HCs. [ABSTRACT FROM AUTHOR]

• Forty patients with focal epilepsy, 40 with IGE, and 40 with FS were included. • ADHD screening was positive in 35% of patients with FS. • ADHD screening was positive in 30% of those with focal epilepsy. • ADHD screening was positive in 10% of patients with IGE. • Adult patients with functional seizures are at high risk of ADHD. We investigated the rates of positive screening for attention deficit-hyperactivity disorder (ADHD) in adults with seizures [i.e., focal epilepsy vs. idiopathic generalized epilepsy (IGE) vs. functional seizures (FS)]. We hypothesized that the rates of positive screening for ADHD are different between these three groups of patients. This was a cross sectional study. Patients, 19 to 55 years of age, with a diagnosis of IGE, focal epilepsy or FS were investigated at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from September 2022 until January 2023 and during their follow-up visits. We used the validated Persian version of Adult ADHD Self-Report Scale (ASRS v1.1)15 to investigate and screen for ADHD in these patients. Forty patients with focal epilepsy, 40 with IGE, and 40 with FS were included. Attention deficit-hyperactivity disorder (ADHD) screening was positive in 35% of patients with FS, in 30% of those with focal epilepsy (compared with FS, p = 0.633), and in 10% of patients with IGE (compared with FS, p = 0.007). Adult patients with functional seizures and those with focal epilepsy are at a high risk of self-reporting experiences that could be characteristic of ADHD. Screening tools [e.g., Adult ADHD Self-Report Scale (ASRS v1.1)] are useful to help clinicians address seizure comorbidities such as ADHD. However, a clinical diagnosis of ADHD should be ascertained in a patient with positive screening. [ABSTRACT FROM AUTHOR]

Background: Evidence on the genetics of functional seizures is scarce, and the purpose of the current scoping systematic review is to examine the existing evidence and propose how to advance the field. Methods: Web of science and MEDLINE were searched, from their initiation until May 2023. The following key words were used: functional neurological disorder(s), psychogenic neurological disorder(s), functional movement disorder(s), psychogenic movement disorder(s), functional seizures(s), psychogenic seizure(s), nonepileptic seizure(s), dissociative seizure(s), or psychogenic nonepileptic seizure(s), AND, gene, genetic(s), polymorphism, genome, epigenetics, copy number variant, copy number variation(s), whole exome sequencing, or next-generation sequencing. Results: We identified three original studies. In one study, the authors observed that six (5.9%) patients with functional seizures carried pathogenic/likely pathogenic variants. In another study, the authors observed that, in functional seizures, there was a significant correlation with genes that are over-represented in adrenergic, serotonergic, oxytocin, opioid, and GABA receptor signaling pathways. In the third study, the authors observed that patients with functional seizures, as well as patients with depression, had significantly different genotypes in FKBP5 single nucleotide polymorphisms compared with controls. Conclusion: Future genetic investigations of patients with functional seizures would increase our understanding of the pathophysiological and neurobiological problems underlying this common neuropsychological stress-associated condition. [ABSTRACT FROM AUTHOR]

Psychogenic nonepileptic seizures (PNES) or functional seizures are universal phenomena. However, data on their epidemiology is limited. The aim of the current study was to review the literature on the epidemiology of PNES and to provide analytical estimates of its incidence and prevalence based on the direct data that are available from previous studies on PNES. The methods of this work had two parts: (1) MEDLINE, PsycINFO, and Scopus from inception to 19 October 2019 were systematically searched. (2) The analytical study of the incidence and prevalence of PNES was performed, based on the following data from previous studies: incidence of PNES, duration of PNES before making a diagnosis, outcome and mortality of PNES. The search strategy yielded five articles; three were on the incidence and two on the prevalence. In the analytical part of the study, the incidence of PNES was calculated to be 3.1 (95% Confidence Interval: 1.1–5.1) per 100,000 population per year. The calculated prevalence rate of PNES in 2019 was 108.5 (95% Confidence Interval: 39.2–177.8) per 100,000 population, in the USA. While, the generalizability of these calculated incidence and prevalence rates to other places in the world is limited, they give us a reasonable hint that PNES is a common condition and the prevalence is much more than that it was thought before. Supplemental data for this article is available online at . [ABSTRACT FROM AUTHOR]

Objective: We searched for, from the FDA (Food and Drug Administration‐USA)‐approved drugs, inhibitors of FKBP5 with tolerable adverse effect profiles (eg, mild headache, sedation, etc.) and with the ability to cross the blood brain barrier (BBB), using bio‐informatics tools (in‐silico). This may pave the road for designing clinical trials of such drugs in patients with functional seizures (FS) and other stress‐associated disorders. Methods: Several databases were used to find all the approved drugs that potentially have interactions with FKBP51 protein [ie, CTD gene‐chemical interaction section of FKBP51 protein of Harmonizome of Mayaanlab, DrugCenteral database, PDID (Protein Drug Interaction Database), DGIdb (the Drug Gene Interaction database)]. Other databases were also searched [eg, clinicaltrials.gov; DRUGBANK (the FASTA format of the FKBP51 protein was imported to the target sequencing section of the database to find the associated drugs), and the STITCH database (to find the related chemical interaction molecules)]. Results: After a comprehensive search of the designated databases, 28 unique and approved drugs were identified. Fluticasone propionate and Mifepristone and Ponatinib, Mirtazapine, Clozapine, Enzalutamide, Sertraline, Prednisolone, Fluoxetine, Dexamethasone, Clomipramine, Duloxetine, Citalopram, Chlorpromazine, Nefazodone, and Escitalopram are inhibitors of FKBP5 and have BBB permeability. Significance: While the current in‐silico repurposing study could identify potential drugs (that are already approved and are widely available) for designing clinical trials in patients with stress‐associated disorders (eg, FS), any future clinical trial should consider the pharmacological profile of the desired drug and also the characteristics and comorbidities of the patients in order to foster a success. [ABSTRACT FROM AUTHOR]

Objective: We investigated the associations between FKBP5 single‐nucleotide polymorphisms (SNPs) and functional seizures (FS). Methods: Seventy patients with FS, 140 with major depressive disorder (MDD), and 140 healthy controls were studied. Their DNAs were analyzed for the rs1360780 in the 3′ region and rs9470080 in the 5′ region of the FKBP5. Childhood trauma questionnaire and hospital anxiety and depression scale were used. Results: Patients with FS and those with MDD had less GG and more AA genotypes in both rs9470080 and rs1360780 SNPs compared with those in healthy controls. Similar results were observed for allelic frequencies. There were no significant differences between FS and MDD groups in terms of genotype and allelic frequencies for both SNPs. The results of multinomial logistic regression analysis showed that FKBP5 polymorphisms were not associated with the diagnosis. Significance: Patients with FS and those with MDD had significantly different genotypes in both rs9470080 and rs1360780 SNPs compared with those in healthy controls. However, it seems that FKBP5 polymorphisms were not associated with FS in the absence of depression. Further genetic investigations of patients with FS may increase our understanding of the neurobiological underpinnings of this condition, but such studies should be large enough and very well designed; they should include a comparison group with depression in addition to a healthy control group. [ABSTRACT FROM AUTHOR]

Objective: We investigated medical comorbidities in patients with functional seizures (FS) and those with epilepsy (idiopathic generalized epilepsies [IGEs] or temporal lobe epilepsy [TLE]). We hypothesized that the nature of medical comorbidities differs between these three groups. This might be helpful to postulate on the pathophysiology of FS. Materials and Methods: In a retrospective study, all adult patients with a diagnosis of IGE, TLE, or FS were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Iran, from 2008 until 2020. The three groups of patients were matched with regard to their age. Age, sex, and medical comorbidities were registered routinely for all patients at the time of the first visit. Results: Nine hundred and sixty-six patients were studied (254 patients with IGE, 467 persons with TLE, and 245 individuals with FS). The groups differed significantly with regard to having medical comorbidities. The most striking difference was comorbid thyroid disorders; this was more common among patients with FS. The diagnosis of FS was independently significantly associated with thyroid disorder comorbidity (odds ratio: 2.77, 95% confidence interval: 1.06-7.23; P = 0.038). Conclusion: Thyroid disorders are significantly associated with FS. We can make the following suggestions to advance the field: a. It is necessary to reproduce this observation in larger multicenter studies; b. We recommend to evaluate thyroid function in all patients with FS; c. It might be helpful to design clinical trials to investigate whether correction of any clinical or subclinical thyroid disorders changes the treatment outcome in patients with FS. [ABSTRACT FROM AUTHOR]

This document is a response to a letter regarding a previous publication on the potential use of FKBP5 blockade for the treatment of stress-associated disorders. The author agrees with the conclusion that more studies are needed to investigate the relationship between FKBP5 and the identified drugs. The in-silico study identified Fluticasone propionate as a potential candidate for future studies, along with Prednisolone, Dexamethasone, and certain psychiatric drugs. Currently, psychotherapy is considered the best treatment option for patients with functional seizures, but there is a need for more effective therapeutic options. The author confirms their responsibility for the manuscript and states that there are no conflicts of interest or funding sources for this research. [Extracted from the article]

• Interactions between genetic factors and sexual trauma may hypothetically contribute to the risk of functional seizures. • Sexual trauma may lead to structural and functional changes in the brain. • These changes may hypothetically predispose patients to functional seizures later in life. The relationship between functional seizures (FS) and sexual trauma has received attention in many previous studies. However, the mechanisms underlying this relationship have not been elucidated yet. The purpose of this narrative review is to explore and speculate on the underpinning neurobiological mechanisms for the association and link between sexual trauma and functional seizures. While existence of a causal relationship between a history of sexual trauma and functional seizures is plausible, it should be viewed and treated as a hypothesis. In explaining this hypothesis, we can speculate that interactions between genetic factors and a history of sexual trauma may contribute to the risk of experiencing functional seizures. Childhood sexual trauma may lead to structural and functional connectivity changes in the brain and dysregulation of the biological stress systems, particularly in women. These neurobiological changes speculatively may predispose patients to functional seizures later in life. Importantly, a history of sexual trauma has many other implications beyond the predisposition towards FS. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the rate of employment in patients with functional seizures (FS) in a follow‐up study. We also investigated the rate of receiving disability benefits in these patients. Finally, we investigated factors that are potentially associated with their employment status. Methods: In this long‐term study, all patients with FS, who were diagnosed at Shiraz Comprehensive Epilepsy Center, Iran, from 2008 to 2018, were investigated. In a phone call interview to the patients in February 2020, we tried to obtain the following information: seizure outcome, employment status, receiving disability benefits, and their current drug regimen, if any. The first call was made in the evening and after working hours. In case of no response, we made two more attempts in the following weeks to contact the patients during different time periods of the day. Results: Eighty‐ four patients participated. Thirty‐one patients (37%) were employed, and 53 people (63%) were not; at the first visit, the rate of employment was 23%. Female sex (Odds Ratio [OR]: 12.18; 95% Confidence Interval [CI]: 3.51–42.18; p =.0001), taking psychiatric drugs (OR: 4.93; 95% CI: 1.17–20.73; p =.02), and being employed previously (OR: 0.19; 95% CI: 0.04–0.77; p =.02) were independently significantly associated with the current employment status. Three patients (4%) reported receiving disability social benefits, two women and one man. Conclusion: This study highlights that unemployment is a serious issue in patients with FS and psychiatric comorbidities play a significant role in the employment status in these patients. [ABSTRACT FROM AUTHOR]

Objectives: This International League Against Epilepsy (ILAE) Report: (a) summarizes the literature about "driving and psychogenic nonepileptic seizures (PNES)"; (b) presents the views of international experts; and (c) proposes an approach to assessing the ability of persons with PNES (PwPNES) to drive. Methods: Phase 1: Systematic literature review. Phase 2: Collection of international expert opinion using SurveyMonkey®. Experts included the members of the ILAE PNES Task Force and individuals with relevant publications since 2000. Phase 3: Joint analysis of the findings and refinement of conclusions by all participants using email. As an ILAE Report, the resulting text was reviewed by the Psychiatry Commission, the ILAE Task Force on Driving Guidelines, and Executive Committee. Results: Eight studies identified by the systematic review process failed to provide a firm evidence base for PNES‐related driving regulations, but suggest that most health professionals think restrictions are appropriate. Twenty‐six experts responded to the survey. Most held the view that decisions about driving privileges should consider individual patient and PNES characteristics and take account of whether permits are sought for private or commercial driving. Most felt that those with active PNES should not be allowed to drive unless certain criteria were met and that PNES should be thought of as "active" if the last psychogenic seizure had occurred within 6 months. Significance: Recommendations on whether PwPNES can drive should be made at the individual patient level. Until future research has determined the risk of accidents in PwPNES a proposed algorithm may guide decisions about driving advice. [ABSTRACT FROM AUTHOR]

• 1492 patients were studied (559 patients with IGE, 646 people with TLE, and 287 persons with FS). • 77 (5.2%) individuals had severe head injuries before the onset of their seizures [9 patients (1.6%) with IGE, 56 people (8.7%) with TLE, and 12 persons (4.2%) with FS; p = 0.0001]. • Compared to people with IGE, the odds ratio of having a premorbid history of severe head injury in the FS group was 2.67 [95% confidence interval (CI): 1.11–6.40; p = 0.0280]. • Compared to people with TLE, the odds ratio of having a premorbid history of severe head injury in the FS group was 0.46 (95% CI: 0.24–0.87; p = 0.0170). The aim of the current study was to compare the frequency of significant head injuries in three groups of people with seizures [idiopathic generalized epilepsies (IGE) vs. temporal lobe epilepsy (TLE) vs. functional seizures (FS)]. This was a retrospective study. All patients with a diagnosis of IGE, TLE, or FS were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2020. One thousand and four hundred ninety-two patients were studied (559 patients with IGE, 646 people with TLE, and 287 persons with FS). Overall, 77 (5.2%) individuals of the studied people reported experiencing severe head injuries before the onset of their seizures [9 patients (1.6%) with IGE, 56 people (8.7%) with TLE, and 12 persons (4.2%) with FS; p = 0.0001]. Compared to people with IGE, the odds ratio of having a premorbid history of severe head injury in the FS group was 2.67 [95% Confidence Interval (CI): 1.11–6.40; p = 0.0280]. Compared to people with TLE, the odds ratio of having a premorbid history of severe head injury in the FS group was 0.46 (95% CI: 0.24–0.87; p = 0.0170). Severe head injury is significantly associated with FS. However, since head injury is also a significant risk factor for focal epilepsies, it may be necessary to ascertain the diagnosis of post-traumatic seizures by obtaing a detailed clinical history and also by performing video-EEG monitoring in order to adopt an appropriate treatment strategy in these patients. [ABSTRACT FROM AUTHOR]

Purpose: We compared various clinical characteristics of pediatric-onset psychogenic nonepileptic seizures (PNES) between patients from five countries. The purpose of this study was to advance our understanding of pediatric-onset PNES cross-culturally.Methods: In this retrospective study, we compared consecutive patients with PNES with an age at onset of 16 years and younger from epilepsy monitoring units in Iran, Brazil, the USA, Canada, and Venezuela. Age, gender, age at seizure onset, seizure semiology, predisposing factors, and video-EEG recordings of all patients were extracted. Pearson Chi-Square, one-way ANOVA and Bonferroni correction tests were used for statistical analyses.Results: Two hundred twenty-nine patients were studied (83 from Iran, 50 from Brazil, 39 from Canada, 30 from the USA, and 27 from Venezuela). Mean age at the onset of seizures was 12.1 ± 3.2 years (range: 4-16 years). The sex ratio of the patients was 1.83: 1 (148 females and 81 males). Clinical characteristics of pediatric-onset PNES showed some significant differences among the nations. However, factors associated with pediatric-onset PNES in these five nations were similar.Conclusion: This study underscores how international cross-cultural studies can make important contributions to our understanding of PNES. Patients with pediatric-onset PNES from different countries were similar on many risk factors associated with PNES. This suggests universality in many features of PNES. However, intriguing differences were also noted with regard to seizure semiology, which might be the result of cultural factors. [ABSTRACT FROM AUTHOR]

The aim of this multicenter international cross-cultural study was to compare clinical variables in a large sample of people with adult-onset psychogenic nonepileptic seizures (PNES). In this retrospective study, we evaluated persons with documented PNES, who were older than 16 years of age at the onset, from four countries (i.e., Iran, Brazil, Venezuela, and Argentina) regarding their age, gender, PNES semiology, and possible predisposing factors. We included 389 patients (244 from Iran, 66 from Brazil, 51 from Venezuela, and 28 from Argentina). Age at diagnosis was 32 ± 9 years (range: 17–64 years), and age at the onset of seizures was 27 ± 8 years (range: 17–49 years). There was a female predominance in all countries. The demographic characteristics and factors associated with PNES were similar among the countries. However, there were significant semiological differences among the countries. This study corroborates the notion that PNES share more similarities than differences cross-culturally and across international borders. However, the background determined by cultural, ethnic, and religious differences may influence the semiology of PNES. Further cross-cultural studies involving more than two continents may advance our understanding of PNES. • We included 389 patients (244 from Iran, 66 from Brazil, 51 from Venezuela, and 28 from Argentina). • There was a female predominance in all countries. • The demographic characteristics and factors associated with PNES were similar among the countries. • However, there were significant semiological differences among the countries. [ABSTRACT FROM AUTHOR]

Sex-related differences have been reported in patients with neurological and psychiatric disorders. It is also plausible to assume that there might be differences between females and males with psychogenic nonepileptic seizures (PNES). In this retrospective study, we investigated patients with PNES, who were admitted to the epilepsy monitoring units at centers in Iran, the USA, Canada, Brazil, Argentina, and Venezuela. Age, sex, age at seizure onset, seizure semiology, factors potentially predisposing to PNES, and video-electroencephalography recording of all patients were registered routinely. Four hundred and fifty-one patients had PNES-only and were eligible for inclusion; 305 patients (67.6%) were females. We executed a logistic regression analysis, evaluating significant variables in univariate analyses (i.e., age, age at onset, aura, presence of historical sexual or physical abuse, and family dysfunction). The only variables retaining significance were historical sexual abuse (p = 0.005) and presence of aura (p = 0.01); physical abuse was borderline significant (p = 0.05) (all three were more prevalent among females). Similarities between females and males outweigh the differences with regard to the demographic and clinical characteristics of PNES. However, notable differences are that females more often report lifetime adverse experiences (sexual and probably physical abuse) and auras. While social, psychological, and genetic factors may interact with lifetime adverse experiences in the inception of PNES, the link is not yet clear. This is an interesting avenue for future studies. • Four hundred and fifty-one patients had PNES-only and were studied. • 305 patients (67.6%) were females. • History of sexual abuse and presence of aura were more prevalent among females. [ABSTRACT FROM AUTHOR]

Objective: We investigated the frequency of reported sexual abuse in patients with psychogenic nonepileptic seizures (PNES) in a Middle-Eastern culture (Iran) and tried to characterize the association between a history of sexual abuse and the clinical characteristics of PNES in these patients.Methods: In this retrospective database study, patients with PNES, who were investigated at Shiraz Comprehensive Epilepsy Center at Shiraz University of Medical Sciences, from 2008 until 2018, were studied. Patients were categorized into two groups: (1) those with a history of sexual abuse and (2) those without such a history.Results: A total of 314 patients were studied. Twenty-six patients (8.3%) had a history of sexual abuse, while 288 patients (91.7%) denied having such an experience. Sex ratio (OR: 3.53; 95% CI: 1.14-10.89; p = 0.02) and a history of child abuse (OR: 4.85; 95% CI: 1.82-12.96; p = 0.002) were significantly associated with a history of sexual abuse.Conclusion: Some people with a history of sexual abuse are at risk of developing PNES later in their lives. While social, cultural, and even genetic predisposition may be interacting for such an association to come to play, there is no concrete direct evidence to clarify this link yet. This should be investigated in future international cross-cultural studies and also highlights the need for planning genetic studies in patients with PNES. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the frequency of dramatic presentations of psychogenic nonepileptic seizures (PNES) (i.e., urine incontinence and ictal injury) and to characterize the patients' historical risk factors that may be associated with such dramatic manifestations.Methods: In this retrospective database study, all patients with PNES, who were investigated at Shiraz Comprehensive Epilepsy Center at Shiraz University of Medical Sciences, from 2008 until 2018, were studied.Results: 259 patients with PNES-only were studied. Thirty-one patients (12%) reported experiencing urinary incontinence. Seventy-five patients (29%) reported having a bodily injury. The associated injuries were as follows: lacerations (35; 13.5%), tongue biting (32; 12%), fractures (5; 2%), burns (2; 1%), and dental injuries (1; 0.5%). Fifty-seven (67%) patients with one of these features and 91 patients (53%) without any of these features were taking antiepileptic drugs; the difference was significant (p = 0.03).Conclusion: Patients with PNES may frequently present with dramatic features including, ictal injury or urinary incontinence, and as a result are at great risk of receiving wrong diagnosis and unnecessary treatments. [ABSTRACT FROM AUTHOR]

Purpose: To compare auras between three groups of people with seizures [i.e., Idiopathic generalized epilepsies (IGE) vs. Temporal lobe epilepsy (TLE) vs. Functional seizures (FS)].Methods: All patients, 10 years of age or older, with a diagnosis of IGE, TLE, or FS were prospectively registered in an electronic database and retrospectively studied at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2020.Results: One thousand and three hundred ninety-one patients were studied (480 with IGE, 617 with TLE, and 294 with FS). Among patients with TLE, 63.5% of individuals reported auras; this figure was 68% in the FS and 12.7% in the IGE groups (p < 0.00001). Odds ratio of having auras in the TLE group compared with the IGE group was 11.96 (95% CI: 8.73-16.39; p = 0.0001). Odds ratio of having auras in the TLE group compared with the FS group was 0.81 (95% CI: 0.61-1.10; p = 0.1840). Odds ratio of having auras in the FS group compared with the IGE group was 14.61 (95% CI: 10.15-21.02; p = 0.0001). The following auras were more frequent among patients with TLE: emotional, cognitive, epigastric, and olfactory/gustatory. The following auras were more frequent among patients with FS: headache and dizziness/vertigo.Conclusion: Auras are not specific to focal epilepsies. Future studies should investigate auras in large cohorts of patients with focal or generalized epilepsies and also those with FS to determine the exact clinical value of each aura. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the driving rate and the rate of road traffic accidents in patients with functional seizures. We hypothesized that road traffic accidents are common in these patients.Methods: In this long-term study, all patients with functional seizures, who were diagnosed at Shiraz Comprehensive Epilepsy Center, Iran, from 2008 until 2018, were investigated. In a phone call interview in February 2020, we obtained the following information: seizure outcome, driving a motor vehicle, experiencing any road traffic accidents in the past 12 months, and their drug regimen.Results: 100 patients participated; 41 patients were driving a motor vehicle in their routine daily lives. Seizure freedom [Odds Ratio (OR): 6.15; 95 % Confidence Interval (CI): 1.95-19.35; p = 0.002] and being employed (OR: 10.66; 95 % CI: 3.03-37.49; p = 0.0001) were significantly associated with driving a motor vehicle. Five patients reported experiencing road traffic accidents while driving a motor vehicle in the past 12 months. All these five patients reported being seizure-free.Conclusion: The majority of patients with functional seizures do not drive a motor vehicle; fear of seizures is a significant determinant. When patients with functional seizures achieve seizure freedom, the rate of driving a motor vehicle increases significantly. The rate of road traffic accidents in patients with functional seizures does not seem to be high. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the sex ratio trajectory across the lifespan in patients with psychogenic nonepileptic seizures (PNES). We hypothesized that there are significant changes in the trajectory of the sex ratio in these patients across the lifespan with respect to the age at onset.Methods: In this retrospective study, all patients with PNES, who were diagnosed at Shiraz Comprehensive Epilepsy Center, Iran, from 2008 until 2019, were investigated. We arbitrarily categorized the patients into five groups according to the age at onset of their PNES [pre-puberty (≤ 14 years), adolescence (15 years to < 19 years), young adulthood (19-25 years), adulthood (26-45 years), and post-menopausal (≥ 46 years)].Results: During the study period, 275 patients with PNES-only had the inclusion criteria. The sex ratios (female to male) of the studied groups according to the age at onset of PNES were as follows: pre-puberty (13:14 = 0.93), adolescence (32:21 = 1.52), young adulthood (54:33 = 1.64), adulthood (71:26 = 2.73), and post-menopausal (7:4 = 1.75). In two-by-two comparison of the group with the lowest sex ratio (pre-puberty) and the group with the highest sex ratio (adulthood) the difference was significant (p = 0.01).Conclusion: We postulate that the higher prevalence of PNES in women may be partly associated with lifetime sex hormone fluctuations; this female preponderance appears during puberty and decreases after menopause. However, most likely this is only one of many potential reasons behind this sex difference; therefore, this is an interesting avenue for future studies. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the current study was to investigate the long-term outcome of patients with psychogenic nonepileptic seizures (PNES) and factors potentially associated with their outcome in Iran.Methods: We investigated all patients with PNES admitted to the epilepsy monitoring unit at the Shiraz Comprehensive Epilepsy Center from 2008 through 2013. Patients included in this study had a confirmed diagnosis of PNES. In a phone call interview to the patients in December 2017, we obtained the following information: seizure outcome (seizure-free during the past 12 months or not), history of receiving any psychotherapy after confirming their diagnosis in the past, and number of psychotherapy sessions the patient had received.Results: Eighty-six patients (54 females and 32 males) met the inclusion criteria. Seventy-four (86%) patients did not receive appropriate psychotherapy. Forty-seven (54.7%) patients were seizure-free during the past 12 months. Age at onset (P = 0.02), education (P = 0.01), and taking psychiatric drugs (P = 0.007) were associated with this outcome.Conclusions: Resources to treat patients with PNES are limited in Iran; however, more than half of the patients became free of seizures. Lower education, comorbid psychiatric problems, and a later age at the onset of seizures may affect the seizure outcome in patients with PNES. Well-designed multi-center cross-cultural long-term studies should address factors associated with outcome in patients with PNES, considering that seizure frequency should not be the only outcome measure. [ABSTRACT FROM AUTHOR]

• Those with late-onset FS were more likely to have medical comorbidities. • Those with late-onset FS more likely had a history of head injury. • Duration of illness was significantly longer in patients with childhood-onset FS. We investigated childhood-onset functional seizures (FS) and late-onset FS and hypothesized that there are differences in their characteristics. In this retrospective study, we investigated all patients with confirmed FS with an age at onset of 14 years or younger and those with an age at onset of 50 years or older, who were admitted to the epilepsy monitoring units at one center in Iran (Shiraz Comprehensive Epilepsy Center, from 2008 until 2022) and one center in the USA (Vanderbilt University Medical Center, from 2011 until 2022). One-hundred and forty patients were included. They included 80 patients with childhood-onset FS and 60 with late-onset FS. Those with late-onset FS were more likely to have medical comorbidities compared with the patients with childhood-onset FS (OR = 13.9). Those with late-onset FS more likely had a history of head injury compared with the patients with childhood-onset FS (OR = 5.97). Duration of illness was significantly longer in patients with childhood-onset FS compared with the patients with late-onset FS (6 years vs. 2 years). Our study identified several similarities and differences in the clinical characteristics and predisposing factors of patients with childhood-onset and late-onset FS. In addition, we found that childhood-onset FS is more likely to remain undiagnosed and thus untreated for many years. These findings provide additional evidence that FS is a heterogenous condition and we propose that a proportion of the differences between patients may be accounted for by age-associated factors. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the frequency and characteristics of auras in patients with psychogenic nonepileptic seizures (PNES) and to characterize the patients' historical and clinical risk factors that may be associated with such manifestations.Methods: In this retrospective database study, all patients with PNES, who were investigated at Shiraz Comprehensive Epilepsy Center at Shiraz University of Medical Sciences, from 2008 until 2018, were studied.Results: During the study period, 258 patients were investigated. One hundred and seventy-three patients (67.1%) reported having auras. Auras were associated with multiple variables, including sex ratio, history of head injury, ictal injury, and taking antiepileptic drugs, in univariate analyses. We then performed a logistic regression analysis, assessing these four variables. The model that was generated by the regression analysis was significant (p = 0.0001) and could predict the possibility of auras in 72% of the patients. Within the model, sex ratio (OR: 0.498; 95% CI: 0.282-0.878; p = 0.01) and a history of head injury (OR: 0.096; 95% CI: 0.020-0.465; p = 0.004) retained their significance.Conclusion: Patients with PNES may frequently report auras including some auras which are often seen in patients with focal epilepsies; as a result, they are at great risk of receiving wrong diagnosis and unnecessary treatments. Health care professionals involved in the management of patients with seizures should be aware of this risk and prescribe an antiepileptic drug only after making a definite diagnosis of epilepsy in a patient with a paroxysmal event. [ABSTRACT FROM AUTHOR]

Abstract Purpose We compared various clinical characteristics of psychogenic nonepileptic seizures (PNES) between young patients from Iran, Saudi Arabia, and Canada, three nations with significantly different socioeconomic and demographic characteristics. This international cross-cultural comparative study may advance our knowledge and understanding of PNES in children and adolescents across the cultures and borders. Methods In this retrospective study, we investigated all patients 16 years of age or younger, with PNES admitted to the epilepsy monitoring units at one center in Iran, one center in Saudi Arabia, and one center in Canada. Age, gender, age at seizure onset, seizure semiology, seizure frequency, factors potentially predisposing to PNES, and video-electroencephalography (EEG) recording of all patients were registered routinely and compared between the nations. Results Fifty-one patients were studied (22 from Iran, 14 from Saudi Arabia, and 15 from Canada). Age at the diagnosis was 13.4 ± 2.2 years (range: 8–16 years), and age at the onset of seizures was 12.3 ± 2.7 years (range: 5–16 years). Demographic and clinical characteristics of and associated factors in the patients among the three nations were not significantly different. Twenty-six (51%) patients were taking antiepileptic drugs at the time of diagnosis; the difference was not statistically significant between the nations (13 patients in Iran, 6 in Saudi Arabia, and 7 patients in Canada; P = 0.5). Conclusion Young patients with PNES across borders and between cultures share more similarities than differences with regard to their demographic and clinical characteristics. Highlights • Fifty-one patients were studied (22 from Iran, 14 from Saudi Arabia, and 15 from Canada). • Age at the onset of seizures was 12.3 ± 2.7 years (range: 5–16 years). • Characteristics of and associated factors in the patients among the three nations were not significantly different. • Young patients with PNES across borders and between cultures share more similarities than differences. [ABSTRACT FROM AUTHOR]

Abstract Purpose The aim of this study was to investigate the frequency of antiepileptic drug (AED) use in patients with psychogenic nonepileptic seizures (PNES) and to characterize the patients' historical risk factors that may be associated with such a practice. Methods In this retrospective database study, all patients with PNES, who were investigated at Shiraz Comprehensive Epilepsy Center at Shiraz University of Medical Sciences, from 2008 to 2018, were studied. Patients with concomitant epilepsy or abnormal Electroencephalogram (EEG) were not included. Results Two hundred and seventy patients had the inclusion criteria; 162 patients (60%) were taking AEDs, and 108 (40%) were not taking any AEDs at the time of the diagnosis. Reporting auras (odds ratio: 0.5; 95% confidence interval (CI): 0.301–0.952; p = 0.03), having ictal or postictal urinary incontinence (odds ratio: 3.86; 95% CI: 1.36–10.94; p = 0.01), reporting a dysfunctional family (odds ratio: 1.75; 95% CI: 1.002–3.072; p = 0.04), and a longer duration of the condition before the diagnosis (odds ratio: 1.057; 95% CI: 1.005–1.112; p = 0.03) were significantly associated with AED use; 63.7% of the cases were correctly predicted by the model that was generated by regression analysis (p = 0.0001). Conclusions Patients with PNES are at great risk of receiving unnecessary AEDs, and some patients' historical factors (e.g., urine incontinence) have a strong association with this practice. Highlights • 162 patients (60%) were taking AEDs, and 108 (40%) were not taking any AEDs at the time of the diagnosis. • Reporting auras (odds ratio: 0.5; 95% CI: 0.301–0.952; p = 0.03) was associated with AED use. • Having ictal or postictal urinary incontinence (odds ratio: 3.86; 95% CI: 1.36–10.94; p = 0.01) was a risk factor. • Reporting a dysfunctional family (odds ratio: 1.75; 95% CI: 1.002–3.072; p = 0.04) was a risk factor. • A longer duration of the condition before the diagnosis (odds ratio: 1.057; 95% CI: 1.005–1.112; p = 0.03) was a risk factor. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate any possible association between education and psychogenic nonepileptic seizures (PNES) and any potential effects education might have on clinical characteristics of patients with PNES.Methods: In this retrospective study, all patients with PNES, who were studied at Shiraz Comprehensive Epilepsy Center at Shiraz University of Medical Sciences, from 2008 until 2018, were recruited. We categorized the patients as 1. Less than 6 years of education; 2. With some college education.Results: Sixty-two patients (19%) had some college education and 38 patients (12%) had less than 6 years of education [22 patients (6.8%) were illiterate]. Age at onset of PNES was earlier in those with some college education (p = 0.0001) and they more often reported a history of sexual abuse (p = 0.02). Other demographic variables, seizure-related variables, PNES associated factors, and use of antiepileptic drugs were not significantly associated with education in the patients (all p values were > 0.05).Conclusions: It seems that the level of education has no significant effects on the clinical picture of PNES (other than its association with age at onset and history of sex abuse). While the above observations are important, they should be investigated in cross-cultural comparisons in future studies to depict a full picture of PNES related factors across borders and cultures. [ABSTRACT FROM AUTHOR]

Purpose We analyzed a series of patients with ictal pain to estimate its occurrence and characterize the underlying etiologies. Methods We retrospectively reviewed all the long-term video-EEG reports from Jefferson Comprehensive Epilepsy Center over a 12-year period (2004–2015) for the occurrence of the term “pain” in the text body. All the extracted reports were reviewed, and patients with at least one documented episode of ictal pain in the epilepsy monitoring unit (EMU) were included in the study. Results During the study period, 5133 patients were investigated in our EMU. Forty-six patients (0.9%) had at least one documented episode of ictal pain. Twenty-four patients (0.5%) had psychogenic nonepileptic seizures (PNES), 10 patients (0.2%) had epilepsy, 11 patients (0.2%) had migraine, and one woman had a cardiac problem. Pain location was in the upper or lower extremities (with or without other locations) in 80% of the patients with epilepsy, 33% of the patients with PNES (p = 0.01), and none of the patients with migraine. Conclusion Ictal pain is a rare finding among patients evaluated in EMUs. Psychogenic nonepileptic seizures are the most common cause, but ictal pain is not specific for this diagnosis. Location of the ictal pain in a limb may help differentiate an epileptic cause from others. [ABSTRACT FROM AUTHOR]

Purpose We compared the semiology of psychogenic nonepileptic seizures (PNES) between patients from the USA and Brazil. This international cross-cultural comparative study may expand understanding of PNES across the borders. Methods We retrospectively investigated all patients with PNES admitted to one epilepsy center in the USA and one in Brazil. We classified their seizures into four classes: generalized motor, akinetic, focal motor, and subjective symptoms. All patients were interviewed by an epileptologist in both countries and were administered psychological assessment measures, including questions about PNES risk factors. For the statistical analyses, we compared patients from the two nations. Results Eighty-nine patients (49 from the USA and 40 from Brazil) were studied. Patients from the two countries were not significantly different with regard to sex and age, but patients from Brazil had earlier age at onset (26 years vs. 34 years; P = 0.004) and a significantly greater delay in diagnosis (9.9 years vs. 5.6 years; P = 0.001). Some characteristics of PNES were different between the two groups; patients from the USA had generally more seizure types and more often reported subjective seizures (55% in the USA vs. 10% in Brazil; P = 0.0001). Clinical and historical characteristics of the patients were not significantly different. Conclusion Delay in diagnosis of PNES may represent a major factor in resource-limited countries. Large multicenter cross-cultural studies may reveal subtle but significant cross-cultural differences with respect to the semiological, clinical, and historical aspects of PNES; however, patients with PNES share more similarities than differences. [ABSTRACT FROM AUTHOR]

Purpose The aim of the current post hoc study was to investigate factors associated with delay in diagnosis of adult patients with psychogenic nonepileptic seizures (PNES). Methods We retrospectively investigated all patients with PNES admitted to the epilepsy-monitoring unit at the Jefferson Comprehensive Epilepsy Center from 2012 through 2016. We identified the median time to diagnosis of PNES and divided the patients into two groups. We studied factors associated with delay in diagnosis of PNES. Results In all, 49 patients (39 women and 10 men) were studied. Mean age at the time of admission was 40 ± 16 years and at the onset of the seizures was 34 ± 16 years. Disease duration was 5.6 ± 8.2 years. The median for time to diagnosis was 3 years. Patients with early diagnosis (before 3 years after seizure onset) (21 patients) and patients with late diagnosis (delay of 3 years or more from onset) (28 patients) were compared. Only history of head trauma had significant association with the delay in diagnosis: 2 of 19 patients (7%) with an early diagnosis and 11 of 28 patients (39%) with a late diagnosis reported head trauma (P = 0.02). Conclusion Delay in diagnosis of PNES is common, and some factors (e.g., history of head trauma) may contribute to this delay. It is important that physicians involved in the management of seizures appreciate the importance of making an early and definitive diagnosis of PNES. [ABSTRACT FROM AUTHOR]

Purpose We classified patients with psychogenic nonepileptic seizures (PNESs) according to a newly proposed classification system. Then, we investigated the demographic and clinical differences between various classes of the patients. Methods We retrospectively investigated all patients with PNESs admitted to the Jefferson Comprehensive Epilepsy Center from 2012 through 2016. We classified the patients into four distinct classes: patients with generalized motor seizures, patients with akinetic seizures, patients with focal motor seizures, and patients with seizures with subjective symptoms. All patients were interviewed by a neuropsychologist and were administered psychological assessment measures, including questions about PNES risk factors. For the statistical analyses, we compared patients who had generalized motor seizures with patients who had nonmotor seizures. Results Sixty-three patients were studied. Thirty-five (55.6%) patients had generalized motor seizures, 14 (22.2%) had seizures with subjective symptoms, 12 (19%) had akinetic seizures, and two (3.2%) patients had focal motor seizures. Patients with generalized motor seizures (35 patients) demonstrated a trend for later age at onset (p = 0.06), more frequently had a history of substance abuse (p = 0.001), and more often had loss of responsiveness with their seizures (p = 0.04) compared with patients who had nonmotor seizures (26 patients). Conclusion The recently proposed PNES classification system is useful and practical. This proposed classification of PNESs may address proper diagnosis and provide standardization across future studies. This may also potentially shed light on the etiologic understanding and management of various classes of patients affected with PNESs. [ABSTRACT FROM AUTHOR]

Purpose Ictal verbal help-seeking has never been systematically studied before. In this study, we evaluated a series of patients with ictal verbal help-seeking to characterize its frequency and underlying etiology. Methods We retrospectively reviewed all the long-term video-EEG reports from Jefferson Comprehensive Epilepsy Center over a 12-year period (2004–2015) for the occurrence of the term “help” in the text body. All the extracted reports were reviewed and patients with at least one episode of documented ictal verbal help-seeking in epilepsy monitoring unit (EMU) were studied. For each patient, the data were reviewed from the electronic medical records, EMU report, and neuroimaging records. Results During the study period, 5133 patients were investigated in our EMU. Twelve patients (0.23%) had at least one episode of documented ictal verbal help-seeking. Nine patients (six women and three men) had epilepsy and three patients (two women and one man) had psychogenic nonepileptic seizures (PNES). Seven out of nine patients with epilepsy had temporal lobe epilepsy; six patients had right temporal lobe epilepsy. Conclusion Ictal verbal help-seeking is a rare finding among patients evaluated in epilepsy monitoring units. Ictal verbal help-seeking may suggest that seizures arise in or propagate to the right temporal lobe. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to describe a series of patients with ictal crying to estimate its occurrence and characterize the clinical features and the underlying etiology. Methods We retrospectively reviewed all the long-term video-EEG reports from Jefferson Comprehensive Epilepsy Center over a 12-year period (2004–2015) for the occurrence of the terms “cry” or “sob” or “weep” in the text body. All the extracted reports were reviewed, and patients with at least one episode of documented ictal crying at the epilepsy monitoring unit (EMU) were included in the study. Results During the study period, 5133 patients were investigated at our EMU. Thirty-two patients (0.6%) had at least one documented seizure accompanied by crying. Twenty-seven patients (26 women and one man) had psychogenic nonepileptic seizures (PNES), and five patients (0.1%) had epilepsy. Among patients with epileptic ictal crying, four patients had focal epilepsy (two had definite, and two had probable frontal lobe epilepsy), while one patient had Lennox–Gastaut syndrome. Conclusion Ictal crying is a rare finding among patients evaluated at the EMUs. The most common underlying etiology for ictal crying is PNES. However, ictal crying is not a specific sign for PNES. Epileptic ictal crying is often a rare type of partial seizure in patients with focal epilepsy. Dacrystic seizures do not provide clinical value in predicting localization of the epileptogenic zone. [ABSTRACT FROM AUTHOR]

Background: We investigated the perceptions of the neurologists practicing in Fars province in Southern Iran about psychogenic nonepileptic seizures (PNES); their diagnostic processes and management strategies. Methods: In this survey, all neurologists participating at the annual meeting of neurologists were asked to participate. These neurologists practice in Fars province. An anonymous questionnaire was specifically developed for this study. Results: About 18 neurologists (14 males and four females), out of 20 attendees, agreed to participate in the study. The mean age of the participants was 41.6 ± 7.5 years. They estimated that 10.8% of patients attending their clinic had seizures or blackouts, whereas 4.4% of patients attending their clinic had PNES. The experiences of the participants about the manifestations that potentially differentiate PNES from epileptic seizures; the tests they use to diagnose suspected patients and their treatment strategies showed significant variability. For example, the tests the neurologists always used for the diagnosis of PNES in suspected patients included routine electroencephalographs (EEGs) by 9 (50%), video-EEG monitoring by 4 (22%), and serum creatine phosphokinase (CPK) measurement by 2 (11%). Conclusion: There is much variability in the approaches to diagnosis and management of PNES in southern Iran. The participants in our study were aware of the many knowledge gaps in this area. [ABSTRACT FROM AUTHOR]

• The most prominent feature of cluster 1 included akinetic seizures. • The most prominent features of cluster 2 included motor seizures and no injury. • The most prominent features of cluster 3 included motor seizures with injury. • Compared to cluster 3, sexual abuse was more often reported by cluster 1. • Compared to cluster 3, physical abuse was less often reported by cluster 2. We applied the Two-Step cluster analysis on a large cohort of patients with functional seizures (FS). We studied whether the background risk factors differed between the patient clusters. All patients with a diagnosis of FS were studied at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2021. The Two-Step cluster analysis was applied considering the age at onset, sex, and seizure semiology. We also studied whether the background risk factors (e.g., a history of sexual abuse, physical abuse, etc.) differed between these patient clusters. Three-hundred and fifty four patients were studied. The Two-Step cluster analysis was applied to the 230 patients who reported any associated risk factors; there were three clusters of patients. The most prominent feature of cluster 1 included akinetic seizures. The most prominent features of cluster 2 included motor seizures and no ictal injury. The most prominent features of cluster 3 included motor seizures with ictal injury. Compared with patients in cluster 3, a history of sexual abuse was more often reported by patients in cluster 1 (OR: 3.26, 95%CI: 1.12–9.47; p = 0.03). Compared with patients in cluster 3, a history of physical abuse was less often reported by patients in cluster 2 (OR: 0.45, 95%CI: 0.22–0.90; p = 0.026). The Two-Step cluster analysis could identify three distinct clusters of patients based on their demographic and clinical characteristics. These clusters had correlations with the associated risk factors in patients with FS. [ABSTRACT FROM AUTHOR]

• The rates of the married status were not significantly different between the two groups. • One hundred and one patients with FS (52%) and 205 PWE (45%) were married (p = 0.104). • In the general population, 64% of all people older than 16 years of age were married. • This rate is significantly higher than the rate of the married status among patients. We investigated the marital status (married vs. none) among patients with seizures [i.e., epilepsy or functional seizures (FS)]. This was a retrospective study of an electronic database of patients with seizures. All young adult patients, 18 to 45 years of age, with a diagnosis of either epilepsy or FS were studied at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2020. The two groups were matched for their age at diagnosis. Age at onset, sex, the marital status, and the final diagnosis were registered routinely. During the study period, 194 patients with FS and 455 patients with epilepsy fulfilled the inclusion criteria. The rates of the married status were not significantly different between the two groups; 101 patients with FS (52%) and 204 PWE (45%) were married (p = 0.103). In the general population in Iran, 42,399,792 out of 66,421,989 (64%) of all people older than 16 years of age were married. This rate is significantly higher than the rate of the married status among patients with FS (p = 0.0006) and also those with epilepsy (p = 0.00001). While the rates of the married status were not significantly different between PWE and those with FS, these rates were significantly lower than that in the general population in Iran. There are intriguing cross-cultural similarities and differences between our observations and those from other nations. These should be investigated in large multicenter international studies in the future. [ABSTRACT FROM AUTHOR]

• One thousand four hundred and ninety-two patients were studied. • In total, 387 patients (25.9%) reported driving a motor vehicle. • Driving rate in IGE was 26.9%, in focal epilepsy was 27.0%, and in FS was 20.3%. • Female sex and a younger age at the onset were associated with not driving. • Being married and having education were inversely associated with not driving. We investigated the rate of driving in patients with seizures [i.e., epilepsy or functional seizures (FS)]. We also investigated the factors that may be associated with NOT driving a motor vehicle. This was a retrospective study of an electronic database of patients with seizures that has been built prospectively over more than a decade. All patients, 20 years of age or older, with a diagnosis of idiopathic generalized epilepsy (IGE), focal epilepsy, or FS were studied at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2020. One thousand four hundred and ninety-two patients were studied (918 patients with focal epilepsy, 338 people with IGE, and 236 individuals with FS). In total, 387 patients (25.9%) reported driving a motor vehicle. Driving rate in patients with IGE was 26.9%, in people with focal epilepsy was 27.0%, and in individuals with FS was 20.3%; the difference was not significant (p = 0.10). Female sex and a younger age at the onset of seizures were significantly associated with not driving a motor vehicle. Being married and having any education were significantly inversely associated with not driving a motor vehicle. Most patients with seizures (either people with epilepsy or those with FS alike) do not drive a motor vehicle in their routine daily lives. Demographic factors (e.g., sex, marital status, and education) have significant associations with not driving a motor vehicle. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the rate of consanguinity of parents of the patients with psychogenic nonepileptic seizures (PNES). This would provide important information for future studies on the potential genetic bases of PNES. In this retrospective study, all patients with PNES, who were studied at Shiraz Comprehensive Epilepsy Center at Shiraz University of Medical Sciences, from 2008 to 2018, were recruited. We categorized the patients as (1) no consanguineous marriage of the parents and (2) with consanguineous marriage of the parents. Three-hundred and sixteen patients had the data on their parental consanguinity available and were studied. The sex ratio (female:male) of the patients was 1.92 (208:108). Parents of 110 (35%) patients had consanguineous marriage, and parents of 206 (65%) patients did not. Demographic variables, seizure-related variables, PNES-associated factors, and the use of antiepileptic drugs were not significantly associated with parental consanguinity in the patients. In this study, we observed that more than one-third of the patients with PNES had parental consanguinity. This rate is very similar to the rate of consanguinity in the general population in Iran. • 316 patients with psychogenic nonepileptic seizures (PNES) were studied. • Parents of 110 (35%) patients had consanguineous marriage. • Parental consanguinity in patients with PNES was not different from that in the general population. • No variable was significantly associated with parental consanguinity in the patients. [ABSTRACT FROM AUTHOR]

• The social aspects of life are important determinants of quality of life. • FS impacts patients across most social aspects of life domains regardless of age. • Multidisciplinary management of FS requires assessment of social aspects of life. The human, as a biological system, is an open system embedded within larger systems —including the family, culture, and socio-political environment. In this context, a patient with functional seizures (FS) is embedded in relationships, educational/professional institutions, culture, and society. Both connection to these broader systems and the quality of these connections, as well as the soundness of each system in and of itself, influence the health and well-being of patients in positive or negative ways. The social aspects of life are important determinants of health and quality of life across the lifespan. The current narrative review brings out several overarching themes in patients with FS. Sections on attachment, marriage, social networking, and stigma highlight the central roles of supportive and affirmative relationships across the lifespan. The section on education underscores the importance of keeping children and youth with FS connected within their school environments, as well as managing any barriers – learning difficulties, school response to FS events, stigma, etc.—that can diminish this connection. Finally, the sections on employment and driving highlight the value of being an active participant in one's society. In summary, FS impacts patients across most social aspects of life domains regardless of age — factors that are important when developing biopsychosocial formulations. This review concludes that the multidisciplinary management of FS requires careful assessment of social aspects of life in patients which can then be targeted for treatment, to improve their quality of life, facilitating recovery, and reducing the risk of relapse. [ABSTRACT FROM AUTHOR]

• Neurologists tended to counsel the patients not to avoid performing all jobs. • More work experience was associated with a similar opinion as above. • Psychiatrists thought that patients should be qualified for disability benefits. In this international study, we aimed to investigate the opinions of physicians dealing with patients with functional seizures (FS) worldwide on working restrictions and disability benefits eligibility. International online survey of neurologists/mental health professionals from Argentina, Venezuela, Colombia, Italy, France, Iran, Iraq, United Arab Emirates (UAE), Qatar, Saudi Arabia, Georgia, and Russia. Six hundred and twenty-seven physicians from 12 countries participated in the study. Working as a neurologist was a predictor to think that patients with FS should not be counseled to avoid performing all jobs or professions as long as they have active disease (OR: 0.46; 95% CI: 0.30 to 0.68; p < 0.001). Having managed more than 200 patients was associated with the opinion that patients should not be counseled to avoid performing any type of work (OR: 2.17; 95% CI: 1.02 to 4.59; p = 0.043). Working as a psychiatrist/psychologist was associated with the idea that patients with FS should be qualified for disability benefits (OR: 1.97; 95% CI: 1.21–3.21; p = 0.006), and receive these benefits lifelong (OR: 0.43; 95% CI: 0.22–0.84; p = 0.014). Neurologists and mental health professionals have different attitudes and opinions toward working restrictions and disability benefits for patients with FS. Further studies should investigate the reasons for these differences, and propose solutions to avoid discrimination and unequal access to employment and disability benefits. [ABSTRACT FROM AUTHOR]

• Four hundred and forty patients were included. • One hundred and twenty six people (30%) had college education, 142 (33%) were employed, and 101 (28%) drove a motor vehicle. • None of the social characteristics of the patients showed significant differences between the groups. To explore various social aspects of life (i.e., employment, education, and driving) in a large sample of patients with functional seizures (FS) living in seven countries from four continents. In this retrospective study, we investigated adult patients with FS, who were admitted to the epilepsy monitoring units at centers in Iran, Qatar, USA, France, Georgia, Egypt, and United Arab Emirates (UAE). We studied the social aspects of life in the whole cohort. Then, we compared the social aspects of life between different world regions. Four hundred and forty patients were included (241 from Iran, 56 from Qatar, 52 from France, 41 from the USA, 19 from UAE, 18 from Egypt, and 13 from Georgia). One hundred and twenty six people (30%) had college education, 142 (33%) were employed, and 101 (28%) drove a motor vehicle in their routine daily lives. People with FS and college education were more likely to report a history of sexual abuse compared with those with a lower education. Patients with no loss of responsiveness with their FS were more likely to be employed. Male patients and patients without aura were more likely to drive a motor vehicle in their routine daily lives. None of the social characteristics of the patients with FS showed significant differences among the two large culturally different groups (Muslim nations vs. Christian nations). It appears that patients with FS across cultures have significant problems in their social aspects of life. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the marital status in a cohort of patients with functional seizures from seven countries in four continents. Factors associated with marital status were also explored. Adult patients with functional seizures who were admitted to the epilepsy monitoring units at centers in Iran, Qatar, USA, France, Georgia, Egypt, and United Arab Emirates (UAE) were retrospectively identified. Marital status was assessed in the whole cohort. Four hundred thirty-two patients were included (241 from Iran, 52 from France, 48 from Qatar, 41 from the USA, 19 from UAE, 18 from Egypt, and 13 from Georgia); 302 were women and 130 were men. One hundred fifty (35%) subjects were single, 245 (57%) were married, and 37 (8%) were separated (31 divorced, 7%; 6 widowed, 1%). Auras with functional seizures were less frequently reported by single people in comparison with that by married patients (54% vs. 61%) [odds ratio (OR) = 0.58]. Separated people compared with those who were married less often had auras with their functional seizures (27% vs. 61%; OR = 0.26) and more often reported a history of sexual abuse (49% vs. 12%; OR = 6.14). The marital status has significant associations with the semiology of functional seizures. A history of sexual abuse is significantly associated with being separated and should be inquired and tackled appropriately during the management process of patients with functional seizures. • Iran: 241 patients, France: 52 , Qatar: 48, USA: 41, UAE: 19, Egypt: 18, and Georgia: 13 patients • One hundred fifty (35%) subjects were single, 245 (57%) were married, and 37 (8%) were separated. • Auras were less frequently reported by single people in comparison with married patients. • Separated people compared with those who were married more often reported a history of sexual abuse. [ABSTRACT FROM AUTHOR]

We conducted a multicenter international cross-cultural comparative study to investigate clinical semiology and predisposing factors of functional seizures in a large cohort of patients living in different countries around the world. We hypothesized that semiology and predisposing factors of functional seizures differ between various world regions. We conducted this retrospective observational study in adults with functional seizures admitted to epilepsy centers in Iran, Qatar, USA, France, Georgia, Egypt, and United Arab Emirates (UAE). We assessed and compared the demographic and clinical seizure characteristics of these patients, according to the patients' reports and review of the ictal recordings during video-electroencephalogram (EEG) monitoring. Five hundred nine patients were included (270 from Iran, 74 from Qatar, 63 from France, 43 from the USA, 22 from Egypt, 20 from UAE, and 17 from Georgia). Although all major manifestations of functional seizures (e.g., aura, loss of responsiveness, generalized motor seizures, ictal injury) were seen in all world regions, seizure semiology differed significantly across countries. Auras, ictal urinary incontinence, and ictal injury were more commonly reported by the American patients than patients from other world regions, whereas loss of responsiveness and generalized motor seizures were more frequently observed in the Iranian and American patients than the European and Arab patients. Semiology of functional seizures seems to vary across various regions of the world; socioeconomic, cultural, ethnic, and religious differences may play an essential role in the modulation of functional seizures semiology across different nations and cultures. • We conducted a multicenter international cross-cultural comparative study of functional seizures. • Frequencies of the investigated clinical characteristics of the patients were different between the world regions. • Frequencies of the risk factors were different between the world regions. • Sociocultural background is probably an important determinant of functional seizures semiology. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the rate of acceptance of functional seizures (FS) or psychogenic nonepileptic seizures (PNES) diagnosis in a cross-sectional study in a cohort from Iran. We hypothesized that the acceptance of FS diagnosis has association with clinical characteristics of the patients.Methods: In this cross-sectional study, all patients with FS, who were diagnosed at Shiraz Comprehensive Epilepsy Center, Iran, from 2008 until 2018, were investigated. In a phone call interview in February 2020, we obtained the following information: whether they have accepted the diagnosis that was delivered to them; what is their seizure outcome (seizure-free during the past 12 months or not).Results: 100 patients participated; at the time of the follow-up call, 74 (74%) patients expressed that they have accepted the diagnosis of FS. At the follow-up call, 48 patients (48%) were seizure-free and 52 patients (52%) were suffering from FS yet; 34 of seizure-free patients (71%) and 40 of those patients who still had seizures (77%) expressed that they have accepted the diagnosis of FS (p = .504; Fisher's exact test). Patients' characteristics and seizure semiology were not associated with the acceptance of the diagnosis of FS.Conclusion: That the majority of patients with FS accept their diagnosis if it is delivered to them appropriately, and demographic and clinical characteristics of the patients do not have associations with this. [ABSTRACT FROM AUTHOR]

• During the study period, 274 patients with PNES-only had the inclusion criteria and were studied. • Seventy-seven (28%) patients had a positive family history of seizures and 197 (72%) patients did not have such a history. • There were no demographic or clinical differences between these two groups. If a positive family history of seizures plays a significant role that contributes to the risk for developing psychogenic nonepileptic seizures (PNES) by means of model learning, one would expect that patients with PNES with a family history of seizures show a different semiology than those without such a history. We investigated whether the above hypothesis is valid. In this retrospective study, all patients with PNES, who were diagnosed at Shiraz Comprehensive Epilepsy Center at Shiraz University of Medical Sciences, Iran, from 2008 until 2019, were investigated. Demographic and clinical characteristics were compared between patients with a positive family history of seizures and those without such a history During the study period, 274 patients with PNES-only had the inclusion criteria. Seventy-seven (28%) patients had a positive family history of seizures and 197 (72%) patients did not have such a history. There were no significant demographic or clinical differences between the two groups. It seems that a positive family history of seizures and model learning does not play a significant role in the development of PNES. Investigators should explore other potentially significant contributors and risk factors for developing PNES in future studies. [ABSTRACT FROM AUTHOR]

We investigated the rate of driving in patients with psychogenic nonepileptic seizures (PNES) from a large cohort in Iran. We hypothesized that these patients commonly do not drive. We also investigated the potential factors that may be associated with driving in these patients. In this retrospective study, all patients with PNES, who were diagnosed at Shiraz Comprehensive Epilepsy Center, Iran, from 2008 until 2019, were investigated. Age, gender, age at seizure onset, seizure semiology and characteristics, driving history reported by the patients, and video-electroencephalography recordings of all patients were registered routinely. During the study period, 221 patients with PNES only had the inclusion criteria and were studied. Forty-eight patients (21.7%) reported that they were driving a car in their routine daily lives. Male sex (odds ratio: 13.2; 95% confidence interval: 4.98–35.45; p = 0.0001) and being employed (odds ratio: 8.08; 95% confidence interval: 3.16–20.69; p = 0.0001) were independently significantly associated with driving. We observed that only about one-fifth of adult patients with PNES reported driving. It is important for the scientific community to develop practice guidelines on how to counsel patients and also the related authorities (e.g., department of motor vehicle authorities) on driving restrictions in people who are affected with PNES. • Forty-eight patients (21.7%) reported that they were driving a car in their routine daily lives. • Male sex (odds ratio: 13.2; 95% confidence interval: 4.98–35.45; p = 0.0001) was significantly associated with driving. • Being employed (odds ratio: 8.08; 95% confidence interval: 3.16–20.69; p = 0.0001) was significantly associated with driving. [ABSTRACT FROM AUTHOR]

The purpose of the study was to review the literature on the terminologies for psychogenic nonepileptic seizures (PNES) and make a proposal on the terminology of this condition. This proposal reflects the authors' own opinions. We systematically searched MEDLINE (accessed from PubMed) and EMBASE from inception to October 10, 2019 for articles written in English with a main focus on PNES (with or without discussion of other functional neurological disorders) and which either proposed or discussed the accuracy or appropriateness of PNES terminologies. The search strategy reported above yielded 757 articles; 30 articles were eventually included, which were generally of low quality. "Functional seizures" (FS) appeared to be an acceptable terminology to name this condition from the perspective of patients. In addition, FS is a term that is relatively popular with clinicians. From the available evidence, FS meets more of the criteria proposed for an acceptable label than other popular terms in the field. While the term FS is neutral with regard to etiology and pathology (particularly regarding whether psychological or not), other terms such as "dissociative", "conversion", or "psychogenic" seizures are not. In addition, FS can potentially facilitate multidisciplinary (physical and psychological) management more than other terms. Adopting a universally accepted terminology to describe this disorder could standardize our approach to the illness and facilitate communication between healthcare professionals, patients, their families, carers, and the wider public. • The search strategy reported above yielded 757 articles. • 30 articles were eventually included, which were generally of low quality. • "Functional seizures" (FS) appeared to be an acceptable terminology from the perspective of patients. • In addition, FS is a term that is relatively popular with clinicians. [ABSTRACT FROM AUTHOR]