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Abstract Objectives We hypothesized that the frequency (in Hertz) of generalized spike–waves (GSWs) in patients with idiopathic generalized epilepsy (IGE) has associations with the syndromic diagnosis as well as with the prognosis of patients (their response to medical treatment). Methods This was a retrospective study of a prospectively developed database. All patients with a diagnosis of IGE were studied at the epilepsy center at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2022. Patients were classified into four IGE syndromes: childhood absence epilepsy; juvenile absence epilepsy; juvenile myoclonic epilepsy; and generalized tonic–clonic seizures alone. Results Five hundred and eighty‐three patients were studied. GSWs were commonly observed in all four syndromes of IGE. Frequency of GSW (in Hertz) did not have a significant association with the syndromic diagnosis of the patients (p = .179). The presence of GSW did not have a significant association with the seizure outcome (becoming seizure free or not) of the patients (p = .416). Frequency of GSW did not have a significant association with the seizure outcome of the patients either (p = .574). Conclusion GSWs are the hallmark electroencephalographic footprints of idiopathic generalized epilepsies; however, neither their presence nor their frequency has practical associations with the syndromic diagnosis of IGEs or their outcome (response to treatment).

Abstract Antiseizure medications (ASMs) constitute the principal of treatment for patients with epilepsy, where long‐term treatment is usually necessary. The purpose of this systematic review is to provide practical and useful information regarding various aspects of the interactions between ASMs and foods and drinks. MEDLINE and ScienceDirect, from the inception to July 15, 2023, were searched for related publications. In both electronic databases, the following search strategy was applied, and the following keywords were used (in title/abstract): “food OR drink” AND “antiepileptic OR antiseizure.” The primary search yielded 738 studies. After implementing our inclusion and exclusion criteria, we could identify 19 studies on the issue of interest for our endeavor. Four studies were identified in the recheck process and not by the primary search. All studies provided low level of evidence. Interactions between foods and ASMs are a common phenomenon. Many factors may play a role for such an interaction to come to play; these include drug properties, administration route, and administration schedule, among others. Drugs‐foods (‐drinks) interactions may change the drug exposure or plasma levels of drugs (e.g., grapefruit juice increases carbamazepine concentrations and the bioavailability of cannabidiol is increased 4–5 folds with concomitant intake of fat‐rich food); this may require dosage adjustments. Interactions between ASMs and foods and drinks may be important. This should be taken seriously into consideration when consulting patients and their caregivers about ASMs. Future well‐designed investigations should explore the specific interactions between foods (and drinks) and ASMs to clarify whether they are clinically important. Plain Language Summary Interactions between antiseizure medications and foods and drinks may be important. This should be taken into consideration in patients with epilepsy.

Abstract Objective The purpose of the current endeavor was to evaluate the feasibility of using easily accessible and applicable clinical information (based on history taking and physical examination) in order to make a reliable differentiation between idiopathic generalized epilepsy (IGE) versus focal epilepsy using machine learning (ML) methods. Methods The first phase of the study was a retrospective study of a prospectively developed and maintained database. All patients with an electro‐clinical diagnosis of IGE or focal epilepsy, at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2022, were included. The first author selected a set of clinical features. Using the stratified random portioning method, the dataset was divided into the train (70%) and test (30%) subsets. Different types of classifiers were assessed and the final classification was made based on their best results using the stacking method. Results A total number of 1445 patients were studied; 964 with focal epilepsy and 481 with IGE. The stacking classifier led to better results than the base classifiers in general. This algorithm has the following characteristics: precision: 0.81, sensitivity: 0.81, and specificity: 0.77. Significance We developed a pragmatic algorithm aimed at facilitating epilepsy classification for individuals whose epilepsy begins at age 10 years and older. Also, in order to enable and facilitate future external validation studies by other peers and professionals, the developed and trained ML model was implemented and published via an online web‐based application that is freely available at http://www.epiclass.ir/f‐ige.

Abstract 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 Objective We aimed to explore the underlying pathomechanisms of the comorbidity between three common systemic autoimmune disorders (SADs) [i.e., insulin‐dependent diabetes mellitus (IDDM), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA)] and temporal lobe epilepsy (TLE), using bioinformatics tools. We hypothesized that there are shared genetic variations among these four conditions. Methods Different databases (DisGeNET, Harmonizome, and Enrichr) were searched to find TLE‐associated genes with variants; their single nucleotide polymorphisms (SNPs) were gathered from the literature. We also did a separate literature search using PubMed with the following keywords for original articles: “TLE” or “Temporal lobe epilepsy” AND “genetic variation,” “single nucleotide polymorphism,” “SNP,” or “genetic polymorphism.” In the next step, the SNPs associated with TLE were searched in the LitVar database to find the shared gene variations with RA, SLE, and IDDM. Results Ninety unique SNPs were identified to be associated with TLE. LitVar search identified two SNPs that were shared between TLE and all three SADs (i.e., IDDM, SLE, and RA). The first SNP was rs16944 on the Interleukin‐1β (IL‐1β) gene. The second genetic variation was ε4 variation of apolipoprotein E (APOE) gene. Significance The shared genetic variations (i.e., rs16944 on the IL‐1β gene and ε4 variation of the APOE gene) may explain the underlying pathomechanisms of the comorbidity between three common SADs (i.e., IDDM, SLE, and RA) and TLE. Exploring such shared genetic variations may help find targeted therapies for patients with TLE, especially those with drug‐resistant seizures who also have comorbid SADs.

Abstract 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 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 Purpose To investigate whether radiologically apparent brain magnetic resonance imaging (MRI) abnormalities are associated with the functional seizure (FS) semiology. Methods All patients with a diagnosis of FS at the epilepsy centers at Shiraz University of Medical Sciences, Iran; Aichi Medical University Hospital, Japan; University of Michigan, USA; University of California, Los Angeles, USA; Emory University School of Medicine, USA; and Hospital el Cruce, Argentina, were studied. Results One hundred patients were included; 77 (77%) had motor functional seizures. Lobar location of brain abnormality did not have an association with the semiology (p = .83). There was no significant difference between ictal behaviors in patients with frontal or parietal lesions compared to those with temporal or occipital lesions. Conclusion There were no associations between functional seizure ictal behaviors and locations of the radiologically apparent brain MRI abnormalities. Further studies are needed to evaluate the underpinnings of varying behaviors in FS.

Abstract 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 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 Video‐encephalographic (vEEG) seizure recordings make essential contributions to the differentiation of epilepsy and psychogenic nonepileptic seizures (PNES). The yield of vEEG examinations can be increased through suggestive seizure manipulation (SSM) (ie, activation/provocation/cessation procedures), but its use has raised ethical concerns. In preparation for guidelines on the investigation of patients with PNES, the ILAE PNES Task Force carried out an international survey to investigate practices of and opinions about SSM. An online questionnaire was developed by the ILAE PNES Task Force. Questions were asked at clinical unit or individual respondent level. All ILAE chapters were encouraged to send questionnaires to their members. The survey was open from July 1, 2019, to August 31, 2019. A total of 487 clinicians from 411 units across 94 countries responded. Some form of SSM was used in 296/411 units (72.0%). Over 90% reported the use of verbal suggestion, over 80% the use of activation procedures also capable of eliciting epileptic activity (hyperventilation or photic stimulation). Only 26.3% of units used techniques specifically intended to provoke PNES (eg, saline injection). Fewer than 10% of units had established protocols for SSM, only 20% of units required written patient consent, in 12.2% of units patients received explicitly false information to provoke seizures. Clinicians using SSM tended to perceive no ethical problems, whereas those not using SSM were likely to have ethical concerns about these methods. We conclude that the use of invasive nocebo techniques intended to provoke PNES in diagnostic settings has declined, but SSM is commonly combined with activation procedures also capable of eliciting epileptic activity. While research suggests that openness about the use of PNES‐specific nocebo techniques does not reduce diagnostic yield, very few units have suggestion protocols or seek patient consent. This could be addressed through establishing consensus guidance for the practice of SSM.

Abstract The COVID‐19 pandemic has changed the face of many practices throughout the world. Through necessity to minimize spread and provide clinical care to those with severe disease, focus has been on limiting face‐to‐face contact. Research in many areas has been put on hold. We sought to determine the impact of the COVID‐19 pandemic on epilepsy research from international basic science and clinical researchers. Responses to five questions were solicited through a convenience sample by direct email and through postings on the ILAE social media accounts and an ILAE online platform (utilizing Slack). Information was collected from 15 respondents in 11 countries by email or via Zoom interviews between May 19, 2020, and June 4, 2020. Several themes emerged including a move to virtual working, project delays with laboratory work halted and clinical work reduced, funding concerns, a worry about false data with regard to COVID research and concern about research time lost. However, a number of positive outcomes were highlighted, not least the efficiency of online working and other adaptations that could be sustained in the future.