Epilepsy & Behavior

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.

Background and ObjectivesIndividuals with disease-causing variants in STXBP1 frequently have epilepsy onset in the first year of life with a variety of seizure types, including epileptic spasms. However, the impact of early-onset seizures and anti-seizure medication (ASM) on the risk of developing epileptic spasms and impact on their trajectory is poorly understood, limiting informed and anticipatory treatment, as well as trial design. MethodsWe retrospectively reconstructed seizure and medication histories in weekly intervals for individuals with STXBP1-related disorders with epilepsy onset in the first year of life and quantitatively analyzed longitudinal seizure histories and medication response. ResultsWe included 61 individuals with early onset seizures, 29 of whom had epileptic spasms. Individuals with neonatal seizures were likely to have continued seizures after the neonatal period (25/26). The risk of developing epileptic spasms was not increased in individuals with neonatal seizures or early infantile seizures (21/41 vs. 8/16; OR 1, 95% CI 0.3-3.9, p = 1). We did not find any ASM associated with the development of epileptic spasms following prior seizures. Individuals with prior seizures (n = 16/21, 76%) had a higher risk to develop refractory epileptic spasms (n = 5/8, 63%, OR =1.9, 95% CI 0.2-14.6, p = 0.6). Individuals with refractory epileptic spasms had a later onset of epileptic spasms (n = 20, median 20 weeks) compared to individuals with non-refractory epileptic spasms (n = 8, median 13 weeks; p = 0.08). When assessing treatment response, we found that clonazepam (n = 3, OR 12.6, 95% CI 2.2-509.4; p < 0.01), clobazam (n=7, OR 3, 95% CI 1.6-6.2; p < 0.01), topiramate (n=9, OR 2.3, 95% CI 1.4-3.9; p < 0.01), and levetiracetam (n=16, OR 1.7, 95% CI 1.2-2.4; p < 0.01) were more likely to reduce seizure frequency and/or to maintain seizure freedom with regards to epileptic spasms than other medications. DiscussionWe provide a comprehensive assessment of early-onset seizures in STXBP1-related disorders and show that the risk of epileptic spasms is not increased following a prior history of early-life seizures, nor by certain ASM. Our study provides baseline information for targeted treatment and prognostication in early-life seizures in STXBP1-related disorders.

IntroductionCatamenial epilepsy refers to a cyclical exacerbation of seizure frequency and/or severity linked to stages of the menstrual cycle. To investigate the contribution of underlying excitatory and inhibitory mechanisms of this exacerbation we induced and measured long-term potentiation (LTP). Oestradiol modulates primarily NMDA receptor driven excitation and would enhance visual LTP. Allopregnanolone modulates GABA receptor mediated inhibition and would suppress visual LTP. MethodA control cohort (n = 25) and a cohort with epilepsy (n = 20) were recruited. Participants took part in a visual LTP task while EEG was recorded. Three study visits were timed to capture the mid-follicular (days +5 to +8), mid-luteal (days -9 to -5) phases, as well as the hormone withdrawal in the perimenstrual phase (days -3 to +2). Blood samples confirmed session timing. Generative computational modelling of thalamocortical changes in the EEG was paired with standard evoked potential analysis. Result17 (age 26 {+/-} 9.40) participants with epilepsy, and a control cohort of 25 (age 30 {+/-} 7.06) without epilepsy completed the study. The P2 visually evoked potential (a positive-going component of the visual event related potential waveform) was significantly more enhanced by LTP induction in the mid-follicular phase than the mid-luteal or perimenstrual phases in the control cohort (F(2, 144) =11.54, p = 0.004 corrected). In contrast, in the epilepsy cohort the P2 was significantly more potentiated in the perimenstrual phase than the mid-follicular or mid-luteal phases (F(2,108) = 12.21, p = 0.005 corrected). The effect of cycle on visual LTP was robust, with only 3/17 participants with epilepsy showing highest P2 modulation in the mid-follicular phase (which is the pattern the healthy cohort showed). The computational modelling showed that in epilepsy, the perimenstrual phase was associated with a decrease in superficial pyramidal grain control as well as decreased LTP driven modulation of feed-forward superficial connections to layer 5 and layer 6 to thalamus. DiscussionOur finding of enhanced visual LTP in the luteal phase and perimenstrual phase of females with epilepsy indicates a breakthrough of glutamatergic excitation. Given the relationship between oestrogen and n-methyl-D-aspartate (NMDA) receptor dependent LTP this is plausibly NMDA receptor driven. Several thalamocortical model parameter changes observed warrant further investigation in studies stratifying participants by catamenial epilepsy type. Overall, while research into allopregnanolone and its inhibitory effects dominate perimenstrual catamenial epilepsy research, this study justifies consideration of the role of seizure exacerbating oestradiol.

ObjectivesThe aim is to assess the knowledge, attitude and practice of the primary school teachers toward. MethodsA descriptive cross-sectional study was conducted among primary school teachers in Khartoum using self-administered, closed ended questionnaires. ResultsAlmost all teachers have heard about epilepsy before. Most of them believed that epilepsy was due to genetic factors (25.4%). (74.6%) of the participants thought that epilepsy was a contagious disease. Concerning practice, (26.5%) of the teachers who did first aid, they carried out all the steps of management truly. ConclusionTeachers generally have some knowledge about epilepsy, but there were also deficiencies in their management measures. Most of them heard about epilepsy from community reflecting the need for training sessions and a national program to raise their awareness and attitude.

Adult hippocampal neurogenesis is disturbed in epilepsy. The increased neuronal activity in the epileptic brain leads to an increased production of newborn cells, increased mossy fibre sprouting and altered integration of new neurons within the hippocampus. Here, we set out to investigate increased astrocyte numbers following status epilepticus. We used immunolabelling of brain sections from the mouse intra-amygdala kainic acid model of epilepsy and publicly available single cell RNA sequencing datasets to assess newborn cells in the dentate gyrus. Similar to published series we found on increased number of reactive astrocytes present in the epileptic hippocampus. Additionally, we identified a cell population that expressed neurogenesis (doublecortin) and astrocyte (glial fibrillary acidic protein) markers in the epileptic brain, both in mouse and in human tissue. We further evaluated the expression profile of these cells. Immunolabelling showed expression of mature astrocyte markers aquaporin 4 and glutamate transporter-1. The single cell RNA sequencing data highlighted expression of neurogenesis and astrocyte markers in the doublecortin/glial fibrillary acidic protein-expressing cells. In conclusion, epilepsy pushes early neuroblasts to fate-switch to an astrocyte lineage as seen in the kainic acid-induced mouse model and in human resected brain tissue. Further understanding how neurogenesis is altered in epilepsy and whether the neuroblast fate-switch can be reverted will help in finding novel therapy strategies for epilepsy and other neurological diseases associated with aberrant adult hippocampal neurogenesis. Key MessagesFollowing kainic acid-induced status epilepticus early neuroblasts appear to undergo a fate-switch to an astrocyte lineage. We were able to confirm the presence of cells positive for early neurogenesis and astrocyte markers in human epileptic tissue using scRNAseq data.

Objectivethe current epilepsy classification is primarily clinical driven and lacks a mechanistic basis. A mechanistic basis of the classification, and within the classification especially the etiology layer, may help to better understand epilepsy and the associated comorbidities. It may also be helpful in guiding epilepsy treatment. With this study we aimed to investigate if there is a modelled mechanistic underpinning for the etiological epilepsy classification by assessing the association between epilepsy etiology and brain network topology. Methodsto that aim we assessed the association between epilepsy etiology and brain network topology. We included children referred to our outpatient first seizure clinic with suspected epilepsy who had a standard interictal EEG recording. From these EEGs, functional networks were constructed based on eyes-closed resting state time-series. Networks were characterized using measures of segregation, integration, centrality, and network strength. Principal component analyses were used to assess whether patients with epilepsy of similar etiology cluster together based on their functional brain network topology. Resultsin total, 228 children with epilepsy were included. Another 402 children served as control subjects. We were not able to detect a correlation between epilepsy etiology and functional brain network topology. We also did not find a difference in brain network topology between the controls and patients with epilepsy. Conclusionsour results do not support the presence of a brain network underpinning for the etiological epilepsy classification. This may support the hypothesis that brain network abnormalities in epilepsy are a result of ongoing seizure activity rather than the epilepsy etiology itself. Further in-depth analyses of network measures and longitudinal studies are needed to confirm this hypothesis.

BackgroundEpilepsy is the most common neurological disorder in children and often requires long-term treatment with valproic acid, which may affect intestinal mucosal resilience. Short-chain fatty acid (SCFA) levels can serve as predictors of gut mucosal integrity in pediatric epilepsy patients undergoing valproic acid therapy. MethodsThis cross-sectional study was conducted at the Pediatric Outpatient Clinic, Department of Child Health, Prof. Dr. R.D. Kandou General Hospital, and Prodia Clinical Laboratory in Manado, from December 2023 to April 2024. Subjects were children with epilepsy aged 6 months to 18 years who met the inclusion criteria. SCFA levels--including total SCFA, acetic acid, propionic acid, and butyric acid--were measured using gas chromatography. ResultsOf the 56 participants, 28 children had received valproic acid therapy for less than one year, and 28 for more than one year. The <1-year therapy group showed significantly higher levels of total SCFA (MD = 4.67 [3.22-6.13]; p < 0.001), acetic acid (MD = 15.53 [12.65-18.41]; p < 0.001), propionic acid (MD = 6.25 [4.16-8.33]; p < 0.001), and butyric acid (MD = 9.53 [7.04-12.02]; p < 0.001) compared to the >1-year therapy group. A statistically significant difference in SCFA levels was observed between the two groups (p < 0.05). ConclusionDuration of valproic acid therapy significantly affects SCFA levels in children with epilepsy.

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.

Neonatal seizures are challenging to diagnose due to subtle clinical presentations and require video-EEG for confirmatory diagnosis. However, video-EEG is not always available, so clinicians must sometimes decide to treat neonatal seizures prior to diagnostic confirmation. The extent of this gap in clinical care is not previously described. This retrospective study examined anti-seizure medication (ASM) use in 115 infants who underwent video-EEG at Mount Sinai. Of 46 infants treated with ASMs, 59% received loading doses before EEG. Among these, 89% showed epileptiform activity and 52% (14/27) had seizures on EEG. Mortality among treated infants was high (30%). These findings highlight the significant reliance on clinical judgment without EEG when treating neonatal seizures. Our data support future work to develop scalable, accessible tools to improve timely and accurate treatment of neonatal seizures.

Patients with drug-resistant epilepsy can experience respiratory alterations notably during seizures. The mechanisms underlying this long-term alteration of respiratory function remain unclear. This study aimed at determining in rats whether epilepsy is associated with alterations of both the respiratory function and brainstem serotonin (5-HT) system. Epilepsy was triggered by pilocarpine-induced status epilepticus in rats. 30-50% of epileptic (EPI) rats exhibited sharp decrease of oxygen consumption (SDOC), low metabolic rate of oxygen and slow regular ventilation; these rats were called EPI/SDOC+ rats. These alterations were only detected in rats with chronic epilepsy, independent of behavioral seizures, persisted over the time, and were not associated with death. In these rats, 5-HT fiber density in the nucleus tractus solitarius was below that of control and EPI/SDOC-rats. Both EPI/SDOC+ rats and DBA/2 mice presenting with fatal respiratory arrest following an audiogenic-induced seizure, a model of sudden and expected death in epilepsy, had increased transcript levels of tryptophan hydroxylase 2 (p<0.001 for both strains) and 5-HT presynaptic transporter (rats: p=0.003; mice: p=0.001). Thus, our data support that 5-HT alterations are associated with chronic and acute epilepsy-related respiratory dysfunctions.

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.

Impaired consciousness is a serious clinical manifestation of epilepsy with negative consequences on quality of life. Little work has investigated impaired consciousness in frontal lobe seizures, a common form of focal epilepsy. In temporal lobe seizures, previous studies showed widespread cortical slow waves associated with depressed subcortical arousal and impaired consciousness. However, in frontal lobe epilepsy, it is not known whether cortical slow waves are present, or whether a very different cortical activity pattern may be related to impaired consciousness. We used intracranial EEG recordings of 65 frontal lobe seizures in 30 patients for quantitative analysis of ictal cortical activity and its relationship to impaired consciousness. Behavioral changes based on blinded review of seizure videos were used to classify focal aware, focal impaired awareness, and focal to bilateral tonic-clonic seizures. Changes in intracranial EEG power from preictal baseline were analyzed in different cortical regions and across frequency ranges in these three categories. We found that frontal lobe focal aware seizures showed approximately 40% increases in intracranial EEG power localized to the frontal lobe of seizure onset across frequency ranges, with relatively smaller changes in other cortical regions. Frontal lobe focal impaired awareness seizures showed approximately 50% increases in intracranial EEG power, not significantly different from focal aware seizures in the frontal lobe of seizure onset (P = 1.038), but significantly greater than focal aware seizures in other broad cortical regions (P < 0.001). Importantly, the widespread cortical increases in EEG power observed in focal impaired awareness versus focal aware seizures were seen not just in the frequency range of slow waves, but were also observed across other frequencies including fast activity. However, the widespread cortical increases in focal impaired awareness seizures differed from focal to bilateral tonic-clonic seizures where intracranial EEG power increased to a much higher level by approximately 600%. The large power increases in focal to bilateral tonic-clonic were significantly greater than in focal impaired awareness seizures both in the frontal lobe of seizure onset and in other cortical regions (P < 0.001). Our findings contrast with focal temporal lobe epilepsy, where impaired consciousness is associated with cortical slow waves. We can speculate that different focal seizure types produce impaired consciousness by impacting widespread cortical regions but through different physiological mechanisms. Insights gained by studying mechanisms of impaired consciousness may be the first step towards developing novel treatments to prevent this important negative consequence of epilepsy.

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.

IntroductionPatients with Neurofibromatosis type 1 (NF1), the most common neurocutaneous disorder, can develop several neurological manifestations that include cognitive impairments and epilepsy over their lifetime. It is unclear why certain patients with NF1 develop these conditions while others do not. Early-life immune activation promotes later-life seizure susceptibility, neurocognitive impairments, and leads to spontaneous seizures in some animal models of neurodevelopmental disorders, but the central nervous system immune profile and the enduring consequences of early-life immune activation on the developmental trajectory of the brain in NF1 have not yet been explored. We tested the hypothesis that early-life immune activation promotes the development of spatial memory impairments and epileptogenesis in a mouse model of NF1. MethodsMale wild-type (WT) and Nf1+/- mice received systemic lipopolysaccharide (LPS) or saline at post-natal day 10 and were assessed in adulthood for learning and memory deficits in the Barnes maze and underwent EEG recordings to look for spontaneous epileptiform abnormalities and susceptibility to challenge with pentylenetetrazole (PTZ). ResultsWhereas early-life immune activation by a single injection of LPS acutely elicited a comparable brain cytokine signature in WT and Nf1+/- mice, it promoted spontaneous seizure activity in adulthood only in the Nf1+/- mice. Early-life immune activation affected susceptibility to PTZ-induced seizures similarly in both WT and Nf1+/-mice. There was no effect on spatial learning and memory regardless of mouse genotype. DiscussionOur findings suggest second-hit environmental events such as early-life immune activation may promote epileptogenesis in the Nf1+/- mouse and may be a risk-factor for NF1-associated epilepsy.

ObjectiveDrug-resistant epilepsy (DRE) poses significant challenges in treatment and management. While seizure-related alterations in peripheral immune players are increasingly recognized, the involvement of the complement system, central to immune function, remains insufficiently explored in DRE. This study aimed to investigate the levels of complement system components and their association with cytokine profiles in patients with DRE. MethodsWe analyzed serum samples from DRE patients (n = 46) and age- and sex-matched healthy controls (n = 45). Complement components and cytokines were quantified using Multi- and Single-plex ELISA. Statistical analyses examined relationships between complement molecules, cytokines, and clinical outcomes including epilepsy duration, Full-Scale Intelligence Quotient (FSIQ) scores, and age. ResultsWe found common alterations in all DRE cases, including significant complement deficiencies (C1q, Factor H, C4, C4b, C3, and C3b/iC3b) and detectable bFGF levels. DRE females showed significantly lower levels of TNF and IL-8 compared to healthy females. We observed a trend towards elevated CCL2 and CCL5 levels in DRE males compared to healthy males. These findings suggest potential sex dimorphism in immune profiles. Our analysis also indicated associations between specific complement and inflammatory markers (C2, IL-8, and IL-9) and Full-Scale Intelligence Quotient (FSIQ) scores in DRE patients. InterpretationOur study reveals sex-specific peripheral complement deficiencies and cytokine dysregulation in DRE patients, indicating an underlying immune system vulnerability. These findings provide new insights into DRE mechanisms, potentially guiding future research on complement and cytokine signaling toward personalized treatments for DRE patients.

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.

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.

Sudden unexpected death in Epilepsy (SUDEP) is the leading cause of death in patients with Epilepsy. Although SUDEP results from cardiorespiratory arrest, its underlying mechanisms are poorly understood. Considering the significant association between stress-related disorders and Epilepsy, we hypothesized that stress exaggerates autonomic reflexes critical in cardiorespiratory function and that these exaggerated reflexes increase susceptibility to SUDEP. Experiments were performed using a novel mouse model of SUDEP where chronic hyperactivity of central corticotropin-releasing hormone (CRH) neurons (Kcc2/Crh) predisposes mice to SUDEP in the weeks following seizure induction based on the ventral intrahippocampal kainate (vIHKA) model of chronic Epilepsy. In our study, the vIHKA model was employed in both wild-type (WT) and Kcc2/Crh mice while they were monitored with EEG and ECG using in vivo telemetry and underwent terminal autonomic reflex testing at time points when mortality peaked and plateaued. A resting tachycardia developed by one week following vIHKA injection but subsided by day 30 in both WT and Kcc2/Crh mice. During spontaneous seizures, Kcc2/Crh mice had more pronounced reflex-like ictal bradycardias compared to WT controls that notably occurred prior ([~]10 sec) to seizure termination. vIHKA injection promoted time-dependent exaggeration of autonomic reflexes, with Kcc2/Crh mice exhibiting robust autonomic disturbances compared to WT controls, including a pronounced serotonin-mediated Bezold Jarisch reflex. Taken together, our findings indicate that increased autonomic disturbance burden parallels time-dependent SUDEP susceptibility in mice with hyperactive stress circuits.

Epilepsy is tightly associated with dysfunction of inhibitory {gamma}-aminobutyric acid (GABA) neurotransmission. In this study, Krushinsky-Molodkina (KM) rats genetically prone to audiogenic seizures (AGS) were used. KM rats are characterized by the development of audiogenic epilepsy during postnatal ontogenesis, with AGS onset at the age of 1.5-2 months and fully developed AGS expression by 3rd month. We analyzed GABAergic system of the inferior colliculi (IC) and the hippocampus of KM rats at different stages of postnatal development. Wistar rats were used as a control. In the IC of young KM rats, Na+/K+/Cl- cotransporter 1 (NKCC1) expression was increased, while in adults K+/Cl- cotransporter 2 (KCC2) was downregulated indicating impairment of postsynaptic GABA action both at early and later stages of postnatal development. In the hippocampus of young KM rats, we observed a decrease in activity of GABAergic neurons and downregulation of KCC2 and NKCC1. Adult rats, in opposite, demonstrated elevated activity of the hippocampal GABAergic cells and unchanged expression of chlorine transporters indicating upregulation of GABA transmission. Thus, GABA dysregulation in the IC can mediate the seizure susceptibility in adult KM rats, while in the hippocampus, upregulation of GABAergic system can restrict the spreading of epileptiform activity from the brainstem.

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.