Epilepsy & Behavior

IntroductionEpilepsy is a common central nervous system disorder characterized by abnormal brain electrical activity. We aimed to compare the metabolic profiles of plasma from patients with epilepsy across different etiologies, seizure frequency, seizure type, and patient age to try to identify common disrupted pathways. Material and methodsWe used data from three separate cohorts. The first cohort (PED-C) consisted of 31 pediatric patients with suspicion of a genetic disorder with unclear etiology; the second cohort (AD-C) consisted of 250 adults from the Estonian Biobank (EstBB), and the third cohort consisted of 583 adults [&ge;] 69 years of age from the EstBB (ELD-C). We compared untargeted metabolomics and lipidomics data between individuals with and without epilepsy in each cohort. ResultsIn the PED-C, significant alterations (p-value <0.05) were detected in sixteen different glycerophosphatidylcholines (GPC), dimethylglycine and eicosanedioate (C20-DC). In the AD-C, nine significantly altered metabolites were found, mainly triacylglycerides (TAG), which are also precursors in the GPC synthesis pathway. In the ELD-C, significant changes in twenty metabolites including multiple TAGs were observed in the metabolic profile of participants with previously diagnosed epilepsy. Pathway analysis revealed that among the metabolites that differ significantly between epilepsy-positive and epilepsy-negative patients in the PED-C, the lipid superpathway (p = 3.2*10-4) and phosphatidylcholine (p = 9.3*10-8) and lysophospholipid (p = 5.9*10-3) subpathways are statistically overrepresented. Analogously, in the AD-C, the triacylglyceride subclass turned out to be statistically overrepresented (p = 8.5*10-5) with the lipid superpathway (p = 1.4*10-2). The presented p-values are FDR-corrected. ConclusionOur results suggest that cell membrane fluidity may have a significant role in the mechanism of epilepsy, and changes in lipid balance may indicate epilepsy. However, further studies are needed to evaluate whether untargeted metabolomics analysis could prove helpful in diagnosing epilepsy earlier.

One third of people with epilepsy (PWE) continue to have seizures despite adequate antiepileptic drug treatment. This condition, known as drug-resistant epilepsy (DRE) significantly impairs their social, family and work environment. The aims of this study were to assess the quality of life (QoL) in PWE with DRE and to investigate which factors are associated with a better QoL. This was a cross-sectional observational study of 133 Latin American PWE. QoL was assessed with the Spanish version of the Quality of Life with Epilepsy questionnaire (QOLIE-10). Independent clinical variables were analyzed with non-parametric statistics and their association with QoL was investigated with multiple linear regression. Poor quality of life was found in 25.8% of PWE. A low number of antiepileptic drugs (AEDs) was the major factor associated with better quality of life, closely followed by seizure frequency. We conclude that careful selection of AED treatment may contribute to improving both seizure control and QoL.

Objective: The postictal state is a major yet underrecognised component of epilepsy burden. We aimed to develop a structured patient-reported instrument to quantify postictal recovery, characterise its multidimensional burden and identify demographic, clinical, psychiatric and treatment-related factors associated with postictal severity and duration. Methods: We conducted a prospective, single-centre observational cohort study (Timone Hospital, Marseille, February 2025 - March 2026). Consecutive patients aged >=15 years admitted for scalp or stereo-EEG video-monitoring were included. Patients completed the Postictal Recovery Scale (PRS), an 11-domain questionnaire assessing fatigue, mood, sensory, motor, language, orientation, time perception and postictal amnesia. Items were rated from 0 (severe impairment) to 3 (no symptoms), yielding a total score of 0-33. Internal consistency was assessed using Cronbach alpha. Associations between PRS scores, subjective postictal duration and covariates were analysed using group comparisons, correlations and regression models. Results: Of 107 enrolled patients, 96 were included. PRS showed good internal consistency (Cronbach alpha; = 0.79). 96% of patients reported experiencing postictal symptoms, with fatigue (80%) and postictal amnesia (79%) being the most frequent and severe manifestations. Recovery exceeded one hour in 21% of patients. Greater postictal impairment was associated with higher interictal anxiety (Spearman {rho} = -0.32, p = 0.0018) and depressive symptoms (Spearman {rho} = -0.40, p = 0.0001), whereas demographic, epilepsy-related and treatment variables showed no significant associations. Altered postictal time perception was reported by 40% of patients and was associated with disorientation, but not psychiatric symptoms. Subjective postictal duration was longer than subjective ictal duration (Wilcoxon test, p < 0.0001). Significance: The postictal state is a frequent and multidimensional patient-reported experience. Greater postictal severity, particularly concerning anxiety and depression, is associated with interictal psychiatric comorbidity, while altered temporal experience emerges as a distinct dimension of postictal dysfunction. These findings support integrating postictal measures into clinical practice and trials.

ObjectiveKCNT1-related epilepsy is an ultra-rare pediatric onset epileptic encephalopathy with a broad clinical phenotype ranging from, most commonly, severe infantile-onset epilepsy and global developmental delay to, less commonly, milder phenotypes including nocturnal seizures, autism spectrum disorder, and learning disability. We initiated the first-ever prospective natural history study to comprehensively clinically phenotype individuals impacted by this disorder. MethodsThe primary study aim was to characterize seizures in individuals with KCNT1-related epilepsy. Secondary and exploratory aims included characterization of the full spectrum of disease symptoms, understanding caregiver burden, and collection of blood and urine samples for biomarker exploration. All study activities were conducted remotely (e.g., home-based assessments, telehealth visits). Results35 participants (n=20 males, 15 females) enrolled in this study. The average age at the baseline visit was 76.0 months old (s.d. = 75.5). This paper presents the study design and methods, presents several challenges that arose in its implementation, and discusses various solutions implemented in this medically complex population. SignificanceFuture work will apply the lessons from the current study in the planning and design of clinical trials for KCNT1-related epilepsy and possibly other developmental and epileptic encephalopathies. HighlightsO_LIKCNT1-related epilepsy is an ultra-rare pediatric onset epileptic encephalopathy with no disease-modifying therapy yet available. C_LIO_LIBecause of its rarity, little is known about the phenotypic range and natural history of symptoms in affected individuals. C_LIO_LITo inform clinical trial planning, we initiated the first ever prospective, longitudinal natural history study of KCNT1-related epilepsy. C_LIO_LIThe unique all-remote design of this study presented various challenges, opportunities, and learnings that will inform future studies. C_LI

Epilepsy is a prevalent condition characterised by recurrent, unpredictable seizures. The diagnosis of epilepsy is by surface electroencephalography (EEG), a time-consuming and uncomfortable process for patients. The diagnosis of seizures using EEG over a brief monitoring period has variable success, dependent on patient tolerance and seizure frequency. Further, the availability of hospital resources, and hardware and software specifications inherently limit the capacity to perform long-term data collection whilst maintaining patient comfort. The application and maintenance of the standard number of electrodes restrict recording time to a maximum of approximately ten days. This limited monitoring period also results in limited data for machine learning models for seizure detection and classification. This work examines the literature on the impact of reduced electrodes on data accuracy and reliability in seizure detection. We present two electrode ranking models that demonstrate the decline in seizure detection performance associated with reducing electrodes. We assert the need for further research in electrode reduction to advance solutions toward portable, reliable devices that can simultaneously provide patient comfort, long-term monitoring and contribute to multimodal patient care solutions.

Epilepsy is one of the most prevalent neurological diseases, with 25-33% of patients developing drug-resistant epilepsy (DRE). The precise etiology of DRE remains unidentified. Recent studies have revealed an increase in tetraploid astrocytes in drug-resistant temporal lobe epilepsy (DR-TLE), a common subtype of DRE. This study aims to characterize the function of tetraploid astrocytes in the brain of subjects without central nervous system diseases and in DR-TLE. Cortical samples adjacent to the epileptogenic zone were obtained from DR-TLE patients undergoing resective neurosurgery and from postmortem donors without neurodegenerative, neurological, or psychiatric disorders. Tetraploid astrocytes were identified using the astrocytic marker NDRG2, and their functional characterization was assessed by evaluating markers of metabolism (ALDH1L1), transport (SOX9), electric function (NF1A), or reactive astrocytes (NF{kappa}B p65 and pSTAT3), via immunostaining followed by flow cytometry. Tetraploid astrocytes expressed all functional markers tested. The percentage of tetraploid astrocytes expressing ALDH1L1 or SOX9 was significantly increased in DR-TLE with respect to controls, whereas NF1A remained unchanged. Inflammatory markers pSTAT3 and NF{kappa}B p65 showed an upward trend in 4C astrocytes. In contrast, diploid (2C) astrocytes expressing these markers were reduced in DR-TLE, suggesting a functional shift toward polyploid cells in the DR-TLE cortex. Our findings suggest the preservation of markers of metabolism, transport and electric function in tetraploid astrocytes in physiological conditions and in DR-TLE patients. Moreover, the astrocytes with metabolic and transporter markers were significantly increased in DR-TLE. These findings point to tetraploid astrocytes as potential contributors to DR-TLE mechanisms.

It is well established that most people with epilepsy experience cyclical fluctuations in seizure susceptibility. These seizure patterns have been associated multiday oscillations in cortical excitability and autonomic changes, although the mechanistic drivers of these cycles are not well understood. In this study, we measured stress hormone levels at phases of seizure cycles to investigate the autonomic system as a possible co-oscillator with multiday cycles of seizure susceptibility. Thirteen participants with focal epilepsy were recruited for this longitudinal study. Participants reported seizures in an electronic diary for >6 months. 24 saliva samples were collected per person across two predicted high risk periods and two predicted low risk periods ("allocated risk"). Saliva samples were analysed for cortisol and dehydroepiandrosterone sulphate (DHEAS) levels. Linear mixed models were fitted to predict stress hormones with fixed effects: multiday seizure cycle (retrospective peak or trough), time of day, allocated risk, perceived stress scale score, and seizure occurrence around the saliva sample time. Participants recorded an average of 193 (SD = 158) seizures during the study period. 312 saliva samples were collected in total. Cortisol levels were significantly higher in the epilepsy cohort compared to the expected general population. On a group level, cortisol was significantly associated with fixed effects time of day and multiday seizure cycle, with cortisol levels heightened at multiday cycle peaks compared to troughs, particularly evident in the morning saliva samples. These results provide new insights into a possible mechanistic driver or co-oscillator of multiday seizure cycles in people with epilepsy, demonstrating that cortisol levels are higher at the peak of multiday cycles irrespective of seizure occurrence. The novel methodology presented in this work may be used to explore interactions between other biomolecules of interest and multiday seizure cycles.

BackgroundAttributional bias, a tendency to overinterpret others intentions as hostile (rather than situational or accidental), represents a component of social cognition and may affect everyday functioning. Neural models link attributional processing to fronto-temporal circuits and the default mode network, which are frequently altered in epilepsy. Difficulties in social participation and employment are common in people with epilepsy, and maladaptive attributional styles may contribute to these challenges. Attributional bias has not been systematically compared across epilepsy syndromes. MethodsWe examined attributional bias in 96 participants comprising 26 individuals with genetic generalised epilepsy (GGE), 27 with temporal lobe epilepsy (TLE), and 43 healthy controls (HC). Attributional style was assessed using the Ambiguous Intentions Hostility Questionnaire. Depressive symptoms were evaluated using the Neurological Disorders Depression Inventory in Epilepsy. Group differences were analysed, and potential clinical and demographical correlates were explored. ResultsThe GGE group exhibited higher hostility bias scores than HC (95% CI: 0.12-0.38, adjusted p = 0.014), whereas the difference between TLE and HC groups was moderate and not statistically significant (95% CI: 0.12-0.58, adjusted p = 0.059). Higher blame scores were positively associated with depressive symptoms (p = 0.016). Disease duration, seizure frequency, and antiseizure medication were not significantly associated with attributional bias. ConclusionsThese findings suggest that some individuals with genetic generalised epilepsy are more likely to interpret ambiguous situations as hostile. Altered attributional style may represent an under-recognised factor contributing to social difficulties in people with epilepsy and warrants further investigation as a potential target for psychosocial interventions. HighlightsO_LISome people with epilepsy are more prone to interpret social situations as hostile. C_LIO_LIHigher depression scores correlate with a tendency to blame external factors for misfortunes. C_LIO_LIDisease duration, antiseizure medication, and seizure frequency do not seem to influence the attributional bias. C_LI

BackgroundResearch suggests that recurrent seizures may lead to neuronal injury. Neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAP) levels increase in cerebrospinal fluid and blood following neuroaxonal damage, and have been hypothesised as potential biomarkers for epilepsy. We examined plasma NfL and GFAP levels and their diagnostic utility in differentiating patients with epilepsy from those with psychogenic non-epileptic seizures (PNES), and other non-epileptic disorders. MethodsWe recruited consecutive adults admitted for video-electroencephalography monitoring and formal neuropsychiatric assessment. Plasma samples were collected on admission. NfL and GFAP levels were quantified and compared between patient groups and an age-matched reference cohort (n=1,926), and correlated with clinical variables. Results149 patients were included. 115 were diagnosed with epilepsy, 22 with PNES and 12 with other conditions. Plasma NfL and GFAP levels were elevated in patients with epilepsy compared to PNES, adjusted for age and sex (NfL p=0.004, GFAP p=0.004). A significantly higher proportion of patients with epilepsy (26%) had NfL levels above the 95th age-matched percentile compared to the reference cohort (5%; p=0.0265). NfL levels above the 95th percentile of the reference cohort had a 97% positive predictive value for epilepsy. DiscussionElevated NfL or GFAP levels may support an underlying epilepsy diagnosis and caution against a diagnosis of PNES alone. Further examination of associations between NfL and GFAP levels and specific epilepsy subtypes or seizure characteristics may provide valuable insights into disease heterogeneity and contribute to the refinement of diagnosis, understanding pathophysiological mechanisms, and formulating treatment approaches.

IntroductionArgininosuccinate lyase is integral to the urea cycle, which enables nitrogen waste and biosynthesis of arginine, a precursor of nitric oxide. Inherited argininosuccinate lyase deficiency causes argininosuccinic aciduria, the second most common urea cycle defect and an inherited model of systemic nitric oxide deficiency. Patients present with developmental delay, epilepsy and movement disorder. Here we aim to characterise epilepsy, a common and neurodebilitating complication in argininosuccinic aciduria. Patients and MethodsWe conducted a retrospective study in seven tertiary metabolic centres in the UK, Italy and Canada from 2020 to 2022 to assess the phenotype of epilepsy in ASA and correlate it with clinical, biochemical, radiological and electroencephalographic data. ResultsThirty-seven patients aged 1 to 31 years old were included. Twenty-two (60%) patients presented epilepsy. Median age at epilepsy-onset was 24 months. Generalized tonic clonic and focal seizures were most common in early-onset patients whilst atypical absences were predominant in late-onset patients. Seventeen patients (77%) required antiseizure medications and 6 (27%) had partially controlled or refractory epilepsy. Epileptic patients presented with a severe neurodebilitating disease with higher rates of speech delay (p=0.04) and autism spectrum disorders (p=0.01) and more frequent arginine supplementation (p=0.01) compared to non-epileptic patients. Neonatal seizures were not associated with a higher risk of developing epilepsy. Biomarkers of ureagenesis did not differ between epileptic and non-epileptic patients. Epilepsy-onset in early infancy (p=0.05) and electroencephalographic background asymmetry (p=0.0007) were significant predictors of partially controlled or refractory epilepsy. ConclusionsEpilepsy in argininosuccinic aciduria is frequent, polymorphic, associated with more frequent neurodevelopmental complications. We identified prognostic factors for pharmacoresistance in epilepsy. This study does not support defective ureagenesis as prominent in the pathophysiology of epilepsy but suggests roles of arginine toxicity and central dopamine deficiency. Key PointsO_LIEpilepsy in ASA is frequent, polymorphic, occurring in early childhood and associated with a more severe neurodevelopmental phenotype. C_LIO_LIEarly-onset epilepsy and electroencephalographic background asymmetry are prognostic for pharmaco-resistance of epilepsy in ASA. C_LIO_LIHyperammonaemia is suggested not to be the primary pathophysiological mechanism for epileptogenesis in ASA. C_LIO_LICentral dopamine deficiency is suggested to have a role in pathophysiology of epilepsy in ASA. C_LIO_LIArginine-related neurotoxicity is suggested to be associated with increased in frequency and severity of epilepsy in ASA. C_LI

ObjectiveSudden unexpected death in epilepsy (SUDEP) has been recognized as an important cause of death in patients with epilepsy. In order to inform patients with epilepsy and their relatives correctly, it is necessary to increase the awareness of students about SUDEP from the early stages of medical education. The aim of this study was to identify the level of knowledge and awareness of medical students in Turkey about SUDEP. MethodsMedical students (23{+/-}7 years old; n=793) in Turkey participated in the online SUDEP awareness survey. The survey included demographic evidence, followed by questions about their awareness of epilepsy, seizure knowledge and about the definition, awareness of SUDEP. ResultsThe majority of medical students (95%) claimed that they had heard about epileptic seizures. Half of the participants (49.9%) mentioned that they had heard about tonic-clonic seizures. However, two-thirds of the students (67%) have never heard about SUDEP, while 85% of the students stated that they did not have sufficient knowledge about SUDEP. Concerning the potential prevention of SUDEP, 80.8% of the students did not know about this topic. Furthermore, most participants (82%) expressed their interest and willingness to learn about SUDEP. ConclusionKnowledge about SUDEP plays a key role in identifying patients at risk and informing patients and their relatives. The limited awareness of SUDEP in medical education may pose risks for patients diagnosed with epilepsy and their relatives, and the effective incorporation of lectures and training in SUDEP into the curriculum of medical school is of paramount importance.

Timely and accurate diagnosis of Psychogenic Non-Epileptic Seizures (PNES) is crucial. Aside from potential diagnostic delays, patients with PNES often undergo unnecessary pharmacological or invasive treatments. Presently, effective bedside tools for distinguishing PNES from epileptic seizures (ES) remain elusive, and the gold standard diagnosis relies primarily on patient history and prolonged video EEG monitoring. In this study, we developed a simple clinical tool - the Mean Dynamic Index (MD) - to differentiate PNES from ES. We divided the body into five anatomical regions: the head and face, two upper extremities, and two lower extremities. Due to limited movement potential, the trunk was excluded from consideration. Among these five areas, only actively involved regions were considered in the score calculation. Each distinct motor feature observed contributed a point to the regional summation, with each regions score comprising the Regional Dynamic Index (RDI). The Mean Dynamic Index (MDI) represents the average of all RDIs. Sixty consecutive patients admitted to the VEEG monitoring unit were evaluated. Of these, 15 patients presented primarily with motor symptoms. Eight were diagnosed with PNES, while seven had epileptic seizures. The mean MDI was 1.2{+/-}0.4 in the PNES group and 2.8{+/-}0.77 in the ES group (p<0.001). The mean MDI/duration ratio was 0.31{+/-}0.38 for PNES and 3.5{+/-}2.4 for ES (p < 0.003). An MDI score of 1.665 yielded a specificity of 87.5% and sensitivity of 100% for diagnosing ES. A low MDI score (<1.66) in motor seizures indicates limited variability in the movement profile of each body part, suggesting a PNES etiology. Additionally, as the MDI/time ratio decreases, PNES becomes more likely. Furthermore, we observed that an RDI of 3 or higher completely differentiated between PNES and ES. These findings offer a valuable bedside tool for distinguishing between the two conditions.

BackgroundEpilepsy research centres in Europe and Asia have reported the correlation between S100 Calcium Binding Protein beta (S100B) and epilepsy. However, whether S100B has clinical diagnostic value has been debated. This epilepsy study developed a long-term research plan to resolve this controversy, divided into three simple phases. MethodsThe first phase is mainly observational studies, focusing on resolving the debate on the correlation between S100B levels in serum or cerebrospinal fluid and epilepsy. The second phase uses observational and randomized controlled research data, focusing on solving the baseline standard of S100B level and epilepsy population with different characteristics and providing a research basis for the predictive value of S100B level on epilepsy. The third phase is mainly based on randomized controlled studies, focusing on the accuracy of S100B as a biomarker for diagnosing epilepsy. DiscussionDue to the large number of high-risk groups for epilepsy, it is difficult to identify whether patients with involuntary jerks of limbs have epilepsy. Although electroencephalogram (EEG) can capture pathological brain waves, it inconveniences the general population. Even when a patient is diagnosed with epilepsy and discharged from the hospital, predicting the time interval for the subsequent seizure is difficult. Therefore, a more convenient and clinically valuable tool than the EEG is necessary. The number of studies on epilepsy biomarkers has gradually increased in recent years, which provides a sufficient research basis for this study. Registrationhttps://www.crd.york.ac.uk/PROSPERO/, CRD-ID: CRD42023425431.

PurposePerinatal ischemic stroke (PIS) is a frequent cause for perinatal brain structure defects resulting in epilepsy, cerebral palsy and disability. Since the severity of symptoms is variable, the aim of this study was to evaluate the outcome of children with PIS and seizures/epilepsy to aid parental counseling and therapy decisions. MaterialWe studied retrospectively patients with arterial PIS and structural epilepsy or seizures in the newborn treated at a single center in 2000-2019. Specifically, signs and symptoms of cerebral palsy (CP), developmental and motor delay, epilepsy and thrombophilia were assessed. ResultsFrom the identified 69 individuals with arterial PIS, we only included the 50 patients (64% male) who had structural epilepsy at the time of investigation or previously in their medical history.The mean age of the included patients was 7.1 years (range 0.08-22) at last consultation. Infarct localisation was predominantly unilateral (86%), left sided (58%) and affecting the middle cerebral artery (94%). Genetic thrombophilia was identified in 52% of the patients examined with genetic testing. More than half of the individuals had CP (52%), and 38.5% had a cognitive outcome below average. First seizures occurred in the neonatal period in 58% of patients and developed into drug-refractory epilepsy in 24.1%. Children with late-onset of epilepsy were twice as likely to develop drug-refractory epilepsy (52.4%). DiscussionOur study shows that patients with PIS and seizures as common sequela often also develop CP. Children with later onset of epilepsy have a worse outcome. Patients with seizure onset in the neonatal period and reccuring seizures have a good response to treatment. Therefore, early diagnosis, follow-up examination and adequate therapy are important. Most children need intensive physiotherapy and speech therapy; however, participation in life is usually age-appropriate.

Background and PurposeWhile the idiopathic generalized epilepsy (IGE) comprise around one fifth of all epilepsy, the pathogenesis of it is largely unknown. Previous studies identified cognitive deficits in IGE patients, nevertheless, whether (and how) the brain structure and functional connectivity (FC) reflect these deficits remains underexplored. Here, we aim to find structural and FC differences in cognitively impaired IGE patients. Materials and MethodsWe recruited 36 IGE patients and 49 matched healthy controls (HC) in this cross-sectional study. All participants underwent structural and resting-state fMRI (rs-fMRI) scanning with a 3 Tesla MRI. Voxel-based morphometric analysis (VBM) was used to assessed structure differences, and seed-based analysis of rs-fMRI was used to examine FC. We examined the cognitive performance of patient with MoCA (Montreal Cognitive Assessment), grouped them into high (HMoCA, >25) and low (LMoCA, [&le;]25) group, and further examined the brain structural changes functional changes in each group. ResultsIGE patients showed right significant decrease in cerebellar gray matter volume (GMV), negatively correlating with the disease duration (r=-0.542, p=0.001), and increase in the left dorsolateral superior frontal gyrus GMV. Right cerebellum showed increased connectivity to the precuneus and angular gyrus, decreased connectivity to the postcentral gyrus and Rolandic operculum. Surprisingly, we found that LMoCA IGE patients (with more cognitive deficits) had increased right nucleus accumbens (NAc) GMV (t = -4.413, p < 0.001) and FC and a stronger NAc - prefrontal cortex FC (t = -2.683, p = 0.013), in comparison with the patients with high MoCA. ConclusionsCognitive impairment in IGE patients is linked to the NAc structural changes and NAc-prefrontal circuit alterations. These results provide novel circuit-level insights into understanding the cognitive impairment in IGE patients, contributing to revealing the pathophysiological mechanisms of IGE.

Background Psychiatric comorbidities commonly have a negative impact on epilepsy outcomes. However, they are continuously ignored in routine epilepsy care, with focus directed more towards seizure control. There is paucity of data on the burden of psychiatric morbidity among those living with epilepsy in Kenya. This study sought to determine the prevalence and associated factors of psychiatric morbidity among patients living with epilepsy at a tertiary referral hospital in Western Kenya. Methods This was a descriptive cross-sectional study. Consecutive sampling was used to recruit participants, with a sample size of 278. Data were collected using a structured pretested sociodemographic and clinical characteristics questionnaire, and the Mini International Neuropsychiatric Interview (MINI), and analyzed using STATA version 16. Pearson Chi-square test/Fishers Exact test and logistic regression were used to assess relationships at bivariate and multivariate levels respectively. Results The prevalence of psychiatric morbidity was 52.2%. Major depressive disorder was the most prevalent (36%), followed by anxiety disorders (26.2%), psychotic disorders (16.9%), and suicidality (15.1%). Casual/self-employment (aOR=2.590, p=0.020), seizure-related physical trauma (aOR=4.032, p=0.004), antiepileptic polytherapy (aOR=4.280, p=0.001), frequent seizures (aOR=3.801, p<0.001), and comorbid medical conditions (aOR=5.478, p=0.047) were independent predictors of psychiatric morbidity. Having attained a tertiary level of education was protective against psychiatric morbidity (aOR=0.221, p=0.036). Conclusion More than half of the patients living with epilepsy had at least one psychiatric comorbidity. Routine psychiatric screening and integration of mental health services in epilepsy care is essential to improve clinical outcomes.

Many patients with epilepsy have inadequate seizure control using current anti-seizure medications (ASMs), illustrating the need for new treatments. Genetic epilepsy syndromes like pathogenic variants in voltage gated sodium channel SCN2A and SCN8A are often poorly controlled by current medications, highlighting the need for better models. Voltage gated sodium channel pathogenic variants that induce epilepsy are often gain-of-function, producing hyperexcitability. We established a fast and precise zebrafish seizure assay using mRNA overexpression of SCN2A and SCN8A variants, which allows rapid screening of both variants and ASMs. These short-term genetic seizure models are assayed in 3 days postfertilization (dpf) larvae. Pathogenic variants of SCN2A and SCN8A produced sporadic seizure behavior. We tested human SCN2A R1882Q, SCN2A R853Q and SCN8A R1872Q pathogenic variants that were identified in epilepsy syndrome patients. These models were used to evaluate the efficacy of 3 ASMs: Topiramate, GS967 and PF-04856264. All 3 epilepsy-associated variants increased seizure activity, and the ASMs significantly decreased this seizure activity. This mRNA overexpression assay successfully evaluates seizure activity induced by variants in voltage gated sodium channel genes and examines ASM efficacy in patient specific pathogenic variants.

ObjectivesWe comprehensively characterised a large paediatric cohort with histologically confirmed focal cortical dysplasia (FCD) type 1 to demonstrate the role of advanced multimodal pre-surgical evaluation and identify predictors of postsurgical outcomes. MethodsThis study comprised a systematic re-analysis of clinical, electrophysiological, and radiological features. The results of this re-analysis served as independent variables for subsequent statistical analyses of outcome predictors. ResultsAll children (N = 31) had drug-resistant epilepsy with varying impacts on neurodevelopment and cognition (presurgical intelligence quotient (IQ)/developmental quotient scores: 32-106). Low presurgical IQ was associated with abnormal slow background electroencephalogram (EEG) activity and disrupted sleep architecture. Scalp EEG showed predominantly multiregional and often bilateral epileptiform activity. Advanced epilepsy magnetic resonance imaging (MRI) protocols identified FCD-specific features in 74.2% of patients (23/31), 17 of whom were initially evaluated as MRI-negative. In six out of eight MRI-negative cases, fluorodeoxyglucose positron emission tomography (FDG-PET) and subtraction ictal single-photon emission computed tomography co-registered to MRI (SISCOM) helped localise the dysplastic cortex. Sixteen patients (51.6%) underwent stereoelectroencephalography (SEEG). Twenty-eight underwent resective surgery, and three underwent hemispheral disconnection. Seizure freedom was achieved in 71.0% of patients (22/31) by the last follow-up, including seven of the eight MRI-negative patients. Anti-seizure medications (ASMs) were reduced in 21 patients, with complete withdrawal in 5 individuals. Seizure outcome was predicted by a combination of the following descriptors: age at epilepsy onset, epilepsy duration, long-term invasive EEG, and specific MRI, and PET findings. SignificanceThis study highlights the broad phenotypic spectrum of FCD type 1, which spans far beyond the narrow descriptions of previous studies. Combining advanced MRI protocols with additional neuroimaging techniques helped localise the epileptogenic zone in many previously non-lesional cases. Complex multimodal presurgical approaches (including SEEG) could enhance postsurgical outcomes in these complex patients. Key pointsO_LIThe phenotypic spectrum of paediatric patients with FCD type 1 spans beyond the narrow description of previous studies C_LIO_LIMRI-negative patients benefit from enhanced precision in localising the epileptogenic zone, facilitated by FDG-PET, SISCOM, and SEEG C_LIO_LIA complex multimodal presurgical approach could enhance postoperative seizure outcomes in patients with FCD type 1 C_LIO_LIPaediatric patients with suspected FCD type 1 should be referred to epilepsy surgery centres as soon as possible C_LI

ObjectiveTo analyze postsurgical outcomes in relation to epilepsy characteristics and genetic etiology in pediatric patients with isolated low-grade epilepsy associated tumors (LEAT) and LEAT plus focal cortical dysplasia type IIIb (FCD IIIb) who underwent epilepsy surgery. MethodsPatients younger than 19 years at the time of epilepsy surgery, with isolated LEAT or LEAT plus FCD IIIb and a minimum follow-up of 2 years were included. Clinical data, neuroimaging, EEG, neuropsychological findings, surgical variables, histopathological and molecular-genetic findings were evaluated. Surgical outcomes were assessed in four domains: seizures, antiseizure medication (ASM) use, cognitive performance changes and complications, including predictor analysis. ResultsSeventy-three children fulfilled the inclusion criteria, with 53 (72.6%) having drug-resistant epilepsy. LEAT plus FCD IIIb were more frequent than isolated LEAT (44/73, 60.3% vs. 29/73, 39.7%) and gangliogliomas were the most common tumor type (43/73, 58.9%), followed by dysembryoplastic neuroepithelial tumor (19/73, 26.0 %). Genetic testing was more frequently positive in isolated LEAT (20/28) than LEAT plus FCD IIIb (18/43, p = 0.02). At the end of follow-up (median 5.7 years), 66 patients (90.4%) were seizure-free, and 57 (78.1%) had discontinued ASM. Younger age at seizure onset, longer epilepsy duration, and a higher number of ASM were correlated to lower pre- and postoperative IQ. An IQ gain of > 10 pts. postoperatively was present in 8 patients (15.1%). Two patients (2.7%) had an unexpected permanent deficit, while 10 (13.7%) had minor temporary deficit. No additional predictive outcome factors were identified. SignificanceEpilepsy surgery yields high chances of freedom from seizures and ASM discontinuation. Early surgical intervention in terms of shorter duration of epilepsy and fewer used ASM can be associated to a higher pre- and postoperative IQ. Molecular-genetic differences between isolated LEAT and LEAT plus FCD IIIb suggest distinct neoplastic and dysplastic entities, respectively. Key pointsO_LIA majority of patients with LEAT achieved freedom from seizures and ASM post-surgically. C_LIO_LIChildren with younger age at seizure onset, longer duration of epilepsy and a higher number of ASM used before surgery had lower pre- and postoperative IQ. C_LIO_LIGenetic cause was detected more often in patients with isolated LEAT vs. LEAT + FCD IIIb implying their neoplastic respectively dysplastic origin. C_LI

Malan syndrome is an ultra-rare Overgrowth-Intellectual Disability syndrome caused by pathogenic NFIX variants, characterized by intellectual disability, postnatal overgrowth, and dysmorphic features. Seizures in Malan syndrome remain poorly understood. We surveyed caregivers of 53 individuals with Malan syndrome. Overall, 55% had seizures or EEG abnormalities. Seizures occurred in 47%, with 28% experiencing drug-resistant epilepsy. The median seizure onset was at age 3 years. Epilepsy classifications included focal (40%) and unknown-onset tonic-clonic seizures (48%). Generalized tonic-clonic (8%), myoclonic (8%), and epileptic spasms (4%) were also reported. Status epilepticus was common (44%). Valproic acid was the most used anti-seizure medication, with variable efficacy. This study represents the largest cohort to date, providing detailed descriptions of seizures in Malan syndrome, and lays a foundation for future research phenotyping epilepsy in affected individuals. Clinicians should maintain a high suspicion of seizures and monitor closely for status epilepticus in individuals with Malan syndrome.