Epilepsy Research

Electroconvulsive therapy (ECT) relies on the electrical induction of generalized seizures to treat major depressive disorder and other psychiatric illnesses. These planned procedures provide a clinically relevant model system for studying neurophysiologic characteristics of generalized seizures. We recently described novel central-positive complexes (CPCs), which were observed during ECT-induced seizures as generalized, high-amplitude waveforms with maximum positive voltage over the vertex. Here, we performed a systematic characterization of 6,928 CPC ictal waveforms recorded in 11 patients undergoing right unilateral (RUL) ECT. Analyses of high-density 65-electrode EEG recordings during these 50 seizures allowed evaluation of these CPCs across temporal, spatial, and spectral domains. Peak-amplitude CPC scalp topology was consistent across seizures, showing maximal positive polarity over the midline fronto-central region and maximal negative polarity over the suborbital regions. Total duration of CPCs positively correlated with the time required for return of responsiveness after ECT treatment (r = 0.39, p = 0.005). The rate of CPCs showed a frequency decline consistent with an exponential decay (median 0.032 (IQR 0.053) complexes/second). Gamma band (30-80 Hz) oscillations correlated with the peak amplitude of CPCs, which was also reproducible across seizures, with band power declining over time (r = -0.32, p < 10-7). The sources of these peak potentials were localized to the bilateral medial thalamus and cingulate cortical regions. Our findings demonstrated CPC characteristics that were invariant to participant, stimulus charge, time, and agent used to induce general anesthesia during the procedure. Consistent with ictal waveforms of other generalized epilepsy syndromes, CPCs showed topographic distribution over the fronto-central regions, predictable intra-seizure frequency decline, and correlation with gamma-range frequencies. Furthermore, source localization to the medial thalamus was consistent with underlying thalamocortical pathophysiology, as established in generalized epilepsy syndromes. The consistency and reproducibility of CPCs offers a new avenue for studying the dynamics of seizure activity and thalamocortical networks.

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

Abstract and key wordsO_ST_ABSObjectivesC_ST_ABSSudden unexpected death in epilepsy (SUDEP) is a leading cause of death for patients with epilepsy; however, the pathophysiology remains unclear. Focal-to-bilateral tonic-clonic seizures (FBTCS) are a major risk factor, and centrally-mediated respiratory depression may increase the risk further. Here, we determined volume and microstructure of the amygdala, a key structure that can trigger apnea in people with focal epilepsy, stratified by presence or absence of FBTCS, ictal central apnea (ICA) and post-ictal central apnea (PICA). Methods73 patients with only-focal seizures and 30 with FBTCS recorded during video EEG (VEEG) with respiratory monitoring were recruited prospectively during presurgical investigations. We acquired high-resolution T1-weighted anatomical and multi-shell diffusion images, and computed neurite orientation dispersion and density imaging (NODDI) metrics in all epilepsy patients and 69 healthy controls. Amygdala volumetric and microstructure alterations were compared between healthy subjects, and patients with only-focal seizures or FBTCS The FBTCS group was further subdivided by presence of ICA and PICA, verified by VEEG. ResultsBilateral amygdala volumes were significantly increased in the FBTCS cohort compared to healthy controls and the focal cohort. Patients with recorded PICA had the highest increase in bilateral amygdala volume of the FBTCS cohort. Amygdala neurite density index (NDI) values were significantly decreased in both the focal and FBTCS groups relative to healthy controls, with values in the FBTCS group being the lowest of the two. The presence of PICA was associated with significantly lower NDI values vs the non-apnea FBTCS group (p=0.004). SignificanceIndividuals with FBTCS and PICA show significantly increased amygdala volumes and disrupted architecture bilaterally, with greater changes on the left side. The structural alterations reflected by NODDI and volume differences may be associated with inappropriate cardiorespiratory patterns mediated by the amygdala, particularly after FBTCS. Determination of amygdala volumetric and architectural changes may assist identification of individuals at risk.

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.

ObjectiveSeizure dogs are service animals trained to respond supportively to seizures in people with epilepsy; some are also trained to detect seizure-specific scents, particularly ictal volatile organic compounds (VOCs). This survey study examines feasibility and safety of incorporating a seizure service dog (SSD) into an inpatient setting, as well as patient perceptions of having an SSD in the Epilepsy Monitoring Unit (EMU). MethodsOur SSD underwent specialized training for seizure response and seizure recognition based on seizure-specific VOCs, and accompanied his epileptologist owner in the EMU on rounds for over four years prior to the study. We administered surveys to patients hospitalized in the EMU before and after interactions with a trained seizure dog. The surveys assessed the patients comfort with the dog, perceived usefulness of service dogs, safety, and tolerability. Select case examples are also presented in which seizure dog spontaneously alerted prior to epileptic seizures; seizures later confirmed by independent EEG review. ResultsPatient responses underscored overall high enthusiasm for seizure dog therapy, with 93% of participants reporting feeling "very comfortable" or "extremely comfortable" with a seizure dog present. No adverse concerns or negative experiences were reported by participants. 91% reported personally experiencing benefits of working with the seizure dog, citing emotional and comfort benefits during their hospitalization. 94% of participants were comfortable with physical contact with the dog or had no proximity preference. ConclusionThese findings suggest that seizure service dogs can be safely integrated into the inpatient EMU setting and have potential to enhance patient care and emotional well-being during EMU monitoring. Summary PointsO_LITotal of 98 patients admitted to EMU were surveyed about opinions regarding seizure dogs and comfort with integration of seizure dog in EMU setting, with 35 patients completing post-test surveys after interacting with the seizure dog. C_LIO_LI93% of surveyed EMU patients completing post-test surveys felt very or extremely comfortable with the seizure dog; no negative experiences or safety concerns were reported. C_LIO_LI91% reported personally experiencing emotional benefits of working with the seizure dog. C_LIO_LISelect case examples demonstrate that the trained seizure dog in our study may be able to spontaneously identify epileptic seizures. C_LI

Access to and delivery of quality surgical epilepsy care remains a challenge in both safety-net and private hospital systems. Underserved populations are more likely to utilize safety-net hospital systems, but there are few data on epilepsy surgery outcomes in this setting. We aimed to analyze and compare surgical epilepsy care in a safety-net versus private hospital system. We prospectively collected evaluation and treatment data in patients undergoing resective surgery for epilepsy at a safety-net hospital system and a collaborating private hospital system between 2010-2017. Seizure characteristics, pre-surgical evaluation, perioperative complications, and seizure outcomes were prospectively recorded. Data from 102 patients in the safety-net and 145 patients in the private hospital system were analyzed. There were higher proportions of African American (p=.02) and Hispanic patients (p= .03) in the safety-net hospital system. There was no difference in mean time from epilepsy onset to surgery between groups (p=.54). The presurgical evaluation was equivalent (p>.18), except for more frequent use of magnetoencephalography in the private system (p=.02). Seizure freedom outcomes were excellent, and complication rates were low with no significant differences between groups (p=.95 and p>.22, respectively). However, patients from safety-net hospital systems were more likely to be lost to follow up (p=.04). Quality and equitable surgical epilepsy care can be delivered in a safety-net hospital system despite the higher-minority demographics and intrinsic factors of safety-net hospitals. Partnership of safety-net hospital systems with established comprehensive epilepsy centers and the expansion of these services is essential for healthcare equity in modern epilepsy care.

AIM: STXBP1-related disorder (STXBP1-RD) is a severe developmental and epileptic encephalopathy characterized by early-onset seizures and persistent cognitive and motor impairments. With disease-modifying trials emerging, a disorder-specific severity scale is needed. To address this, we adapted a validated clinician-reported measure from CDKL5 Deficiency Disorder to develop the STXBP1 Clinical Severity Assessment (S-CSA) and evaluated its psychometric properties. METHOD: The S-CSA was adapted from the CDKL5 Clinical Severity Assessment through expert consensus sessions with STXBP1 clinicians. Revisions addressed gaps in motor and vision domains, adding tremor and vision items. The measure was administered to 123 individuals with STXBP1-RD. Psychometric evaluation included confirmatory factor analysis, internal consistency, composite reliability, average variance extracted, and distinctiveness, compared with recommended thresholds. RESULTS: Analyses supported a three-domain structure (motor, communication, vision) with factor loadings >0.5 and strong internal consistency (Cronbachs alpha >0.7; composite reliability >0.88). Model fit and variance metrics met recommended standards, and domains demonstrated distinctiveness. No ceiling or floor effects were observed. Minimal skew was seen in motor (0.34) and communication (0.16) domains; positive skew in vision (2.2) was seen, identifying patients with and without cortical visual impairment. INTERPRETATION: The S-CSA demonstrates strong validity and reliability in STXBP1-RD and may show utility in clinical trials for STXBP1-RD and potentially other severe DEEs. Key Words: STXBP1-Related Disorder, Developmental and Epileptic Encephalopathies, Clinical Outcome Assessments

BackgroundComplete resection of focal malformations of cortical development (MCD) has been recognized as crucial for the success of epilepsy surgery. However, many of these lesions escape detection using even state-of-the-art epilepsy protocol MRI imaging. This study evaluates the concurrence of radiographic and histopathologic findings of MCD in patients with refractory temporal lobe epilepsy (TLE) and defines the predictive value of EEG findings in the detection of MCD. Materials and MethodsPre-operative MRI, scalp VEEG, and post-operative surgical pathology reports from 34 consecutive patients treated for refractory TLE by surgical resection over a ten year period were included in analysis. Radiographic findings of MCD were correlated with histopathologic findings of MCD and compared against pre-operative interictal scalp EEG findings. Results66.7% of focal cortical dysplasias (FCD) identified on pathology and all cases of mild MCD (mMCD) were missed on pre-operative MRI. The description of a rhythmic or continuous interictal abnormality on pre-operative VEEG corresponds to a sensitivity of 73.1% and a specificity of 62.5% in detecting either FCD or mMCD. Of the patients who had a radiographically occult FCD, 80% had either a continuous or rhythmic interictal abnormality described in the interpretation of their pre-operative VEEG. ConclusionThis study highlights the high prevalence of MCDs in refractory TLE and the high rate of missed MCDs on pre-operative MRI. Findings here suggest that pre-operative scalp EEG may be able to provide additional information in the pre-operative detection of MCDs and therefore inform surgical decision making.

BackgroundEpilepsy is the second most common and frequently encountered neurological disorder which poses huge threat to known healthcare systems worldwide also causing financial, socio economic burden to the community. Complex Partial Seizures are a form of focal epileptic seizures that may impair consciousness. Aim and objectivesOur motivation for the study was to understand the extent of patients with complex partial seizures associated with medial temporal lobe sclerosis. Materials and methodsWe performed a cross sectional study about patients with complex partial seizures in Thanjavur medical college and hospital about their clinical profile and neuro-radiological correlation. Statistical analysis and resultsThrough our multimodal study with EEG, MRI on N=118 (female / male, age range, Most common age group-10-20 years, mean age of 23 years, SD-14 years, 66% males), we observed that atypical febrile seizures and fever provoked seizures has more association (18%) to complex partial seizures and to medial temporal lobe sclerosis in comparison to 12% in an earlier study. ConclusionWe believe this study summarizes the complex partial seizure features, origin, and their link to Medial Temporal lobe Sclerosis in our subject pool from Thajavur, India. LimitationThere are some limitations to our study, especially with no video EEG monitoring and no invasive EEG recording. We aim to improve them in our future studies.

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.

Patients with focal temporal lobe seizures often experience loss of consciousness. In humans, this loss of consciousness has been shown to be positively correlated with EEG neocortical slow waves, similar to those seen in non-REM sleep. Previous work in rat models of temporal lobe seizures suggests that decreased activity of subcortical arousal systems cause depressed cortical function during seizures. However, these studies were performed under light anesthesia, making it impossible to correlate behavior, and therefore consciousness, to electrophysiologic data. Further, the genetic and molecular toolkits allowing for precise study of the underlying neural circuitry are much more developed in mice than in rats. Here, we describe an awake-behaving, head-fixed mouse model of temporal lobe seizures with both spared and impaired behavior reflecting level of consciousness. Water-restricted mice were head-fixed on a running wheel and trained to associate an auditory stimulus to the delivery of a drop of water from a dispenser. To investigate the effect of seizures on behavior, seizures were electrically induced by stimulating either the left or right hippocampus via a chronically-implanted electrode, while mice were performing the task. Behavior was measured by monitoring lick responses to the auditory stimulus and running speed on the wheel. Further, local field potentials (LFP) signals were simultaneously recorded from hippocampus and orbitofrontal cortex (OFC). Induced focal seizures were 5-30s in duration, and repeatable for several weeks (n=20 animals). Behavioral responses showed a decrease in lick rate to auditory stimulus, and decreased running speed during seizures (p<0.01, n=20 animals). Interestingly, licking response to sound could vary from being impaired to normal during seizures. We found that behavioral impairment is correlated with large amplitude cortical slow-wave activity in frontal cortex, as seen in patients with temporal lobe seizures. These results suggest that induced focal limbic seizures in the mouse can impair consciousness and that the impaired consciousness is correlated with depressed cortical function resembling slow wave sleep. This novel mouse model has similar characteristics with previously studied rat models and human temporal lobe seizures. By leveraging the genetic and molecular techniques available in the mouse, this model can be used to further uncover fundamental mechanisms for loss of consciousness in focal seizures.

BackgroundThe goal of this systematic review is to assess the published literature for seizure risk with chloroquine therapy in persons with and without epilepsy. With the COVID-19 pandemic, there is a desperate need for therapy against the SARS CoV-2 virus. Chloroquine is one proposed medication that has received substantial public attention. However, drug labeling in the package insertion states that persons with epilepsy have the risk of chloroquine provoking seizures, and this has increased questions and anxiety in the epilepsy community. MethodsPubMed (1970 to March 27, 2020) and the Embase (1970 to March 27, 2020) were searched with the terms chloroquine and seizure or epilepsy. Selected studies were reviewed, and the adverse drug reaction was classified. ResultsOnly nine out of 27 studies were deemed eligible for systematic analysis. Out of the nine studies, only one was a prospective study (N=109), two were case series (N=6), and the remaining 6 were case reports. The dose of chloroquine ranged between 100-500 mg/day, except in one patient, the seizure was after taking 1000 mg. The strength of causality for the drug causing seizures in healthy and persons with epilepsy was mostly possible or unlikely, and none were certain. The only clinical trial that evaluated seizure risk with chloroquine failed to find any significant relation. ConclusionAlthough the drug insertion label states an increased risk of seizure, the systematic review highlights that such a statement is not supported by any class I studies but by anecdotal case reports. The only randomized clinical study revealed that seizures were not associated with an increased blood level of chloroquine or its metabolite. The present systematic review should provide reassurance to busy clinicians and persons with epilepsy that chloroquine, if prescribed to treat COVID-19, lacks any substantial evidence to suggest that the medication increases the risk of seizure.

BackgroundDespite the central role of the temporal lobes in conceptual processing, the impact of temporal lobe epilepsy (TLE) on semantic knowledge remains unclear. ObjectivesThis systematic review and meta-analysis aimed to investigate semantic functioning in TLE and the impact that seizure lateralisation and surgical intervention have on semantic outcomes. MethodologyA comprehensive literature search was conducted using Medline, Embase, and PsychINFO. Studies were eligible if they included participants aged [&ge;]18 years with TLE and evaluated semantic functioning. Risk of bias was assessed using the Newcastle-Ottawa scale, and a narrative synthesis summarised the review findings. Meta-analyses compared semantic performance across individuals with TLE and healthy controls and left and right TLE. Results141 studies, encompassing 8,241 participants (TLE: n = 5,623, controls: n = 2,618), were included, reporting over 30 different semantic measures. Both narrative review and meta-analysis showed significantly poorer semantic performance in people with TLE compared to controls, with impairments in semantic fluency (g = -1.35), WAIS-IV Vocabulary (g = -1.08), and Camels and Cactus Test (g = -1.37), but not on Pyramids and Palm Trees (g = -0.44). Some lateralisation effects were evident, with verbal semantic impairments more prominent in left TLE. ConclusionsTLE is associated with a mild semantic impairment. While left-sided lesions are associated with worse verbal semantic impairment, lateralisation effects more broadly were mild and inconsistent. Our findings emphasise the need to conduct routine semantic assessments in TLE to support more precise cognitive deficit monitoring, better-informed surgical risk discussions, and the development of personalised rehabilitation plans. HighlightsTLE is commonly associated with a mild impairment in semantic functioning. LTLE is generally associated with relatively poorer performance on verbal-based semantic measures. However, both LTLE and RTLE tend to demonstrate impairment across both verbal- and visual-based semantic measures. In sum, semantic measures should be included in routine cognitive evaluations to support the clinical care of individuals with TLE.

We examined seizure semiology and response to medications in 28 children (9 female, 19 male) with likely pathogenic and pathogenic SCN2A-related epilepsy. Parents reported seizure onset, seizure semiology, genetic variants, therapies used for seizures, and response to treatment. 27 children experienced defined seizures and 1 reported no seizure history. The most common initial seizures were focal or hemi-convulsions (n=8). Tonic seizures were the most common reported seizure type while febrile and atonic or drop seizures were the least common. Most patients experienced multiple seizures daily or were entirely seizure-free, with no difference based on age at seizure onset. The proportion of effective trials of the 8 most commonly reported medications ranged from 4 of 26 trials (levetiracetam) to 5 of 10 trials (valproic acid). Phenytoin was the most commonly reported effective treatment (N=4). Topiramate was reported to be the most effective treatment in combination with another treatment (N=6). We found a wide phenotypic spectrum of SCN2A-related disorders and a possible correlation between genotype and seizure onset, semiology, and treatment response. Gain-of-function mutations in early-onset SCN2A epilepsies responded well to sodium channel blockers. Further exploration of SCN2A pathogenic variants are needed to identify mediation mechanisms of action in SCN2A-related epilepsy.

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.

Key points1. Antiseizure medications may change how strongly seizures synchronise with seizure cycles estimated from seizure diaries. 2. One seizure rate can be produced by different seizure cycles, suggesting a one-to-many relationship between seizure rate and cycles. 3. Using seizure cycles to time medication and assess efficacy could prove challenging with paper-based monitoring due to the complexity of cycles and potential drug effects. A seizure cycle tracking algorithm combined with an electronic seizure diary might support this task. Evaluating effectiveness of anti-seizure medications in epilepsy often relies on seizure frequency, reported through seizure diaries before and after treatment initiation. Measuring efficacy with seizure frequency can be challenging and unreliable as seizures tend to occur in cyclical patterns-- seizure cycles--making it difficult to distinguish drug effects from natural fluctuations. Incorporating cycle information could aid treatment evaluation, but antiseizure medications (ASMs) may alter seizure cycles, warranting further study. We conducted an observational study using seizure and ASM tracking app data (Feb. 2023) from 86 individuals with epilepsy. Participants were grouped based on ASM regimen and [&ge;]50% seizure rate reduction at 4 months after a drug change (drug-switching-responders, n=7/45; drug-switching-non-responders, n=38/45) or random timepoint (drug-sustained-responders, n=8/41; drug-sustained-non-responders, n=33/41). We compared groups on three seizure cycle variables detected via diaries: 1. how strongly seizures synchronise with a cycle, measured by the Synchronisation Index (SI), 2. cycle period, and 3. number of detected cycles. Permutation tests (=0.05, p<0.004 with Bonferroni correction) assessed significance, and regression models examined correlations with seizure rate. Across an average 612-day study period, 22,976 seizures were reported. Following an ASM change, the SI of the seizure cycle was more likely to change (p<0.004). This was pronounced in drug-switching-responders (median absolute SI difference: 0.37 [IQR=0.26] vs. 0.11 [IQR=0.11] in the drug-sustained-responders, p<0.004, permutation test). Changes in cycle length and number of detected cycles were similar across groups, possibly due to a non-linear relationship between seizure rate and cycles, suggested by weak linear correlations and poorly fitting models. These findings suggest ASMs may influence how strongly seizures synchronise with diary-detected seizure cycles. However, this relationship is complex and not yet well understood, complicating clinical interpretation. Ongoing research into real-time seizure cycle tracking may support the use of seizure cycles in aiding treatment monitoring.

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.

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.

ObjectivesDevelopmental and epileptic encephalopathies (DEEs) caused by pathogenic variants in SCN8A are associated with difficult-to-treat and early-onset seizures, developmental delay/intellectual disability, impaired quality of life, and increased risk of early mortality. Commonly used antiseizure medications (ASMs) for SCN8A-related disorders, caused by gain-of-function variants, are sodium channel blockers. The use of such ASMs is often not enough to gain satisfactory seizure control. In this retrospective study, the effect of cenobamate was assessed in patients with SCN8A-DEE. MethodsAcross multiple centers and through a collaboration with the patient advocacy organization International SCN8A Alliance, patients with SCN8A-DEE treated with cenobamate for [&ge;]3 months were identified. Data were obtained once from patients caregivers or treating physicians through a RedCap survey. The functional effects of the included patients SCN8A variants were determined by functional tests published in the literature or functionally classified by prediction tools. ResultsTwelve patients (2-25 years, 8 females) with presumed gain-of-function SCN8A variants were treated with cenobamate for a mean period of 8.6 months (range 3-27 months). Countable motor seizures were reduced in 12/12 (100%) patients. Seven experienced a seizure reduction above 75% of which two patients achieved seizure freedom. A 25-50% and 50-75% decrease was observed in three and two patients, respectively. An increase in seizure-free days/patient was also reported. Rescue medication was decreased in 83% of patients, and non-seizure-related improvements (increased alertness, better sleep, improved muscle tone) were observed in 58%. Adverse effects were reported by 33%; half resolved spontaneously or by the reduction of concomitant ASMs. SignificanceOur data suggest, that cenobamate is a promising and safe treatment for SCN8A- DEE, even during early infancy. As a possible precision approach to treatment, cenobamate effectively reduced seizure burden and ameliorated non-seizure-related symptoms. Similar results may be achieved in cohorts of patients with gain-of-function variants encoding other sodium channels. Key pointsO_LIPatients with DEE caused by pathogenic GOF variants in SCN8A are commonly treated with sodium channel blockers, often without satisfying seizure control. C_LIO_LIAdjunctive cenobamate improved seizure frequency in 12/12 patients (2-25 years, 8 females) with SCN8A-DEE of which two achieved seizure freedom. C_LIO_LIAn increase in seizure-free days/patient, non-seizure-related improvements (e.g. increased alertness), and a decrease in rescue medication was also observed. C_LIO_LICenobamate is a promising and safe treatment for SCN8A-DEE, even during early infancy. C_LIO_LISimilar results may be achieved in patients with gain-of-function variants encoding other sodium channels. C_LI

Absence seizures are episodes of impaired consciousness and responsiveness that impact an individuals ability to interact with the world around them. Childhood absence epilepsy, a condition defined by these seizures, can have profound effects on childrens social, educational, and psychological development. Absence seizures are accompanied by a distinctive electrographic signature called a spike-wave discharge. The impairment of consciousness associated with a spike-wave discharge can be variable: some people maintain responsiveness during some absence seizures, and some rodent oscillations resembling spike-wave discharges may not have any behavioral impact. We previously observed that spike-wave discharges in the Genetic Absence Epilepsy Rat from Strasbourg model sometimes terminated shortly after presentation of a conditioned auditory stimulus. In this study we found that these terminations were caused by the stimuli and that they occurred after approximately 50% of stimuli. We also found that the probability of a spike-wave discharge being interrupted depended on stimulus timing, degree of conditioning, and electrographic signal power. These data provide insight into the factors that determine the mechanisms of absence seizure termination, with possible implications for therapy.