Epilepsy & Behavior

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

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.

Early acquired brain injury is a major risk factor for infantile epileptic spasms syndrome (IESS), which may impair cognitive development, especially if diagnosis and treatment are delayed. However, individual-level prediction of which infants will develop IESS is currently not possible. We assessed whether high-frequency oscillations (HFOs) in scalp EEG or recurrent interictal epileptiform discharges (IED) during the first months of life could predict forthcoming IESS. Our population-based cohort included 36 infants with cortical injury due to infarction, haemorrhage, infection or trauma involving a large cortical area ([&ge;] anterior/posterior cerebral artery territory or [&ge;] half of the middle cerebral artery territory), or hypoxic-ischaemic encephalopathy with cortical and deep grey matter involvement. The infants underwent repeated EEGs during the first year of life until 12 months of age or until IESS diagnosis. HFOs during sleep were scored both visually and automatically, whereas IEDs were assessed visually only. We tested whether HFO rate increased during the first year of life using a mixed-effects model with within- and between-subject random effects. Using only EEGs recorded prior to IESS diagnosis, we evaluated whether HFO rate or recurrent IEDs could predict IESS development by training a ridge-regularized logistic regression model with exhaustive leave-2-subjects-out cross-validation. Eleven infants (31%) developed IESS. HFO rate increased with age in both groups but more steeply in the IESS group [within person slope {beta} = 2.43 (IESS) vs. 0.06 (no-IESS) units/month, P < 0.001]. The logistic regression model showed that both HFO rate [AUC 0.801 (95% CI 0.668, 0.936)] and recurrent IEDs [AUC 0.826 (95% CI 0.720, 0.932)] were able to predict forthcoming IESS. However, in a multivariable model, only recurrent IEDs remained independently associated with IESS, and HFO rate did not add predictive value. The marked increase in HFO rate toward IESS diagnosis supports their role as a biomarker of epileptogenesis. During the first months of life, HFOs and recurrent IEDs performed equally well in predicting subsequent IESS. However, IEDs are easier to apply to clinical practice.

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

Objective Memory impairment is a frequent comorbidity of focal epilepsy, incompletely explained by seizure frequency or structural pathology. Ictal and postictal hippocampal dysfunction disrupt memory processes, but their cumulative impact remains poorly quantified. This study introduces cumulative hippocampal seizure-related burden metrics and examines their association with long-term memory consolidation. Methods Twenty consecutive patients undergoing stereo-EEG in Marseille (2016-2018) were prospectively included. Continuous stereo-EEG recordings between two memory assessments (30 minutes and one week post-encoding) were analysed. Hippocampal ictal involvement and durations were assessed using epileptogenicity markers and visual stereo-EEG analysis. The postictal period was quantified using permutation entropy. Cumulative hippocampal seizure-related burden metrics (ictal, postictal and combined: c-HipSZB) were computed across hippocampus-involving ictal events. Verbal and visual memory were assessed using standardized recall and recognition tasks. Associations were examined using univariate and multivariate analyses. Results Higher dominant-hemisphere hippocampal burden was associated with poorer one-week verbal memory (performance and retention), independently of most covariates. Higher c-HipSZB was associated with lower total recall performance (RT; free + cued) and RT retention ({beta} = -25.04 and -23.88; R2 = 0.57 and 0.53; p < 0.05) and accounted for the greatest variance in both outcomes (adjusted R2= 0.59 and 0.53; {beta} = -25.45 and -24.27; p < 0.01), particularly when adjusting for epilepsy duration. No robust associations were observed between non-dominant-hemisphere hippocampal seizure-related burden metrics and visual memory. Effects predominantly involved recall. Interpretation Cumulative ictal-postictal hippocampal dysfunction is a major determinant of impaired long-term verbal memory consolidation in focal epilepsy.

Objective Temporal lobe encephaloceles (ENC) are underdiagnosed causes of drug-resistant temporal lobe epilepsy (TLE), frequently associated with idiopathic intracranial hypertension (IIH). Emerging evidence suggests glymphatic system dysfunction in both IIH and TLE. We investigated glymphatic markers in TLE associated with ENC compared with seizure-free postoperative TLE controls of different aetiology. Methods Surgical specimens from 13 patients with TLE-ENC and 12 TLE-control patients were analyzed. Histological glymphatic markers included aquaporin-4 (AQP4), glial fibrillary acidic protein (GFAP), podoplanin (PDPN), perivascular space (PVS) enlargement, and vessel density. High resolution MRI was used to assess a global PVS score. Results Compared with TLE-controls, TLE-ENC specimens showed increased white matter AQP4 expression and AQP4/GFAP ratio, whereas the AQP4/GFAP ratio was reduced in grey matter. PDPN expression was significantly elevated in both grey and white matter in TLE-ENC cases. MRI demonstrated greater supratentorial PVS enlargement in in ENC patients. Radiological features suggestive of IIH were identified in 46.1% of TLE-ENC patients. Compared with controls, TLE-ENC patients had shorter disease duration and lacked association with previous febrile seizures. Surgical treatment achieved seizure freedom in 70% of ENC patients at a median follow-up of 32 months. Interpretation This study provides the first characterization of glymphatic alterations in TLE-ENC-related epilepsy. Dysregulation of AQP4 and PDPN together with increased PVS burden suggests a distinct glymphatic dysfunction pattern in TLE-ENC, supporting a potential pathophysiological link among ENC formation, IIH, and epileptogenesis mediated by altered cerebrospinal fluid dynamics.

Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE) is a recently recognized cause of drug-resistant focal epilepsy. It is often MRI-negative or shows imaging features mimicking focal cortical dysplasias, which makes recognition difficult and limits presurgical counseling. We aimed to identify an intracranial EEG (iEEG) biomarker that distinguishes MOGHE from other developmental brain lesions encountered in epilepsy surgery. In a retrospective multicenter test cohort of 38 patients (18 MOGHE, 20 non-MOGHE), we analyzed long-term stereo-EEG and subdural recordings. Only MOGHE patients showed highly stereotyped clusters of very brief low-voltage fast activity (LVFA) events, organized into status-like 3 to 12-minute episodes that often lacked clear clinical symptoms. LVFA clusters were present in 16/18 MOGHE and 0/22 non-MOGHE patients. We then tested diagnostic performance in an independent, blinded single-center validation cohort of 22 patients (11 MOGHE, 11 non-MOGHE), in which visual identification of LVFA clusters correctly classified 10/11 MOGHE and 10/11 non-MOGHE cases (Cohens kappa=0.82). Penalized logistic regression further confirmed MOGHE histology as the strongest predictor of LVFA clusters, independent of age and lobe localization. Because LVFA clusters can be recognized visually on routine intracranial EEG recordings without specialized software, this biomarker is readily applicable in clinical practice and may improve presurgical identification of MOGHE. Future prospective studies should determine whether its recognition influences surgical planning, improves outcome prediction, or facilitates selection of patients for mechanism-based therapies.

Introduction Language functional MRI (fMRI) is a valuable tool for presurgical planning in epilepsy. Functional MRI can be challenging in children, and head motion can compromise its utility. The candidacy of patients with ADHD for fMRI is sometimes queried regarding concerns about possible head motion. In 2020, we implemented an fMRI task training program, via telehealth and/or mock MRI. We aimed to determine whether training increased language lateralisation success and/or reduced head motion in all patients, and in those with ADHD. We also aimed to determine whether patients with ADHD exhibited more head motion during fMRI than those without ADHD. Methods We retrospectively identified 223 epilepsy (85%) and other neurosurgery patients, (241 scans including repeats) with language fMRI at Royal Children's Hospital, Melbourne, Australia, 2016-2024. There were 24 individuals with ADHD listed in the Electronic Medical Record, five of whom had diagnoses of both ADHD and autism; and nine with autism. Language lateralisation success was determined by clinician description recorded as left/right/bilateral in the medical record. 99 patients were provided the training including fMRI task practise. Head motion was quantified by maximum Framewise Displacement (FDmax; mm). Results ADHD was associated with lower language lateralisation success. Training was associated with greater language lateralisation success, across all patients, and in those with ADHD. Regarding ADHD and head motion, outliers in FDmax were seen in 5 young patients with ADHD. Data were trimmed to allow separate investigation of FDmax for the sample with and without extremes of head motion. In untrimmed data, FDmax was significantly higher in patients with ADHD than in those without. In trimmed data, FDmax was on average lower in patients with ADHD than those without, however this was not statistically supported. Regarding training and head motion, across all patients, FDmax was significantly lower for scans with training than without. In patients with ADHD, FDmax was on average lower for scans with training, however training was not associated with FDmax. Conclusions Language fMRI training was associated with higher language lateralization success, particularly in patients with ADHD. Training was associated with reduced head motion across all patients. Although some young patients with ADHD had substantial head motion, most in our sample did not move more than those without ADHD. We conclude that the training program increases success of language fMRI, and that an ADHD diagnosis should not be a contraindication to language fMRI.

Temporal lobe epilepsy (TLE) is a heterogeneous disorder with most clinical presentations involving unilateral or bilateral hippocampal seizure onsets. Antiseizure medications are often ineffective for TLE, and epilepsy surgery can have variable outcomes. Risk factors for TLE are readily identifiable and typically precede chronic epilepsy, providing a window of opportunity for preventative treatments. However, there are currently no clinically approved anti-epileptogenic therapies. In this study, we investigate the role of Wnt signaling in epileptogenesis using two mouse TLE models, the intrahippocampal kainate model of unilateral TLE (IHK), and the intraperitoneal kainate model of bilateral TLE (IPK). We specifically examined adult-born immature dentate granule cells as these cells have been heavily implicated in the pathogenesis of TLE and clinical TLE is typically initiated in adulthood. We observed that adult-born immature dentate granule cells undergo pathological morphological changes during epileptogenesis in both the IHK and IPK models of TLE. When compared across epileptogenic zones, however, these changes differed between the two models. Wnt signaling also decreased in these cells in epileptic mice during the epileptogenic period. When mice were treated with SB415286, a highly selective Wnt activator, Wnt signaling in immature dentate granule cells was restored to baseline levels and pathological remodeling changes were reduced in both models. These data therefore suggest that a reduction in Wnt signaling in immature dentate granule cells plays an etiological role in epileptogenesis, and that restoring Wnt signaling using Wnt activating drugs or alternative agents may have therapeutic potential as an anti-epileptogenic strategy in TLE.

Epilepsy is characterized by widespread structural brain alterations extending beyond the epileptic zone, involving both cortical and subcortical regions. Importantly, the clinical manifestation of epilepsy, including seizure types, psychiatric comorbidities, and treatment responses, has been shown to differ between sexes. However, sex differences in structural alterations in epilepsy have been seldomly reported in neuroimaging studies, partly due to limited sample sizes and single-center designs. Here, we systematically investigated sex differences in common epilepsies and their related clinical variables using structural neuroimaging biomarkers in an international multi-center cohort of 1,253 epilepsy patients and 1,077 healthy controls. We studied cortical thickness and subcortical volume in two types of epilepsy: temporal lobe epilepsy (TLE) and genetic generalized epilepsy (GGE). Both male and female patients with TLE showed widespread cortical and subcortical thinning compared with controls. In GGE, when compared separately to controls, male patients showed only subtle structural alterations, whereas female patients exhibited more widespread structural alterations. Sex-stratified analyses revealed some variation in the extent and distribution of cortical thickness and subcortical volume alterations between male and female patients in both epilepsy cohorts. Yet, we did not find significant sex-by-diagnosis interaction effects in TLE and GGE. Similarly, no significant interaction effects were observed between sex and age of onset or disease duration in either patient group. Overall, although we observed some differences in regional cortical thickness and subcortical volume between male and female patients with epilepsy, we did not find significant sex-by-diagnosis interactions. Our findings indicate that sex differences in behavioral and clinical outcomes of epilepsy may involve biological or functional processes that require further investigation.

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

Gain-of-function variants (GOF) in SCN8A, which encodes the NaV1.6 sodium channel, lead to epilepsy syndromes ranging from drug-responsive self-limited (SeLIE) and intermediate epilepsy to drug-resistant developmental and epileptic encephalopathy (DEE). It is currently unclear why individuals with SCN8A GOF variants show variable responses to sodium channel blockers (SCBs). Here, we compared the clinical characteristics of 173 individuals with 25 different SCN8A GOF variants following the hypothesis that carriers of variants affecting activation gating respond less well to SCBs than those with variants affecting fast inactivation gating, given that use-dependent SCBs preferentially target inactivated channel states. We found that individuals with variants altering channel activation gating were more severely affected than those with variants altering inactivation properties: They had an earlier age at onset (3 vs. 5 months, P < 0.0001), higher prevalence of DEE (75% vs. 39%; P < 0.0001), and poorer response to SCBs (20% vs. 69% seizure free; P < 0.0001). We performed pharmacological studies on representative and recurrent variants from each group: two variants (F846S and M1760I) causing hyperpolarizing shifts of the voltage-dependent activation curves, and two variants (G1475R and N1877S) causing depolarizing shifts of the voltage-dependent fast inactivation curves. Phenytoin failed to suppress neuronal firing in neurons expressing activation-related variants, but showed good suppressing effects in neurons expressing inactivation-related variants. In contrast, PRAX-330, a new SCB, which showed much faster binding rates than phenytoin, was effective for both groups of variants by markedly reducing neuronal firing through rapidly and persistently stabilizing NaV1.6 in the inactivated state. Our findings provide new insights into the mechanism of drug-resistance in SCN8A-DEE and support PRAX-330 and compounds with similar pharmacological properties as a promising preclinical candidate for targeted therapies.

AbstractO_ST_ABSBackgroundC_ST_ABSInvasive neuromodulation may be used in patients if seizure medications fail and surgery is not an option. However, moderate success is achieved and improved paradigms are required. The medial septum has been considered a suitable target for the treatment of temporal lobe epilepsy due to its location and connectivity. ObjectiveTo assess the effect of medial septum low-frequency deep brain stimulation to inhibit pentylenetetrazole (PTZ)-induced seizures. MethodsMale Sprague-Dawley rats were stereotaxically implanted in the medial septum and left dorsal hippocampus one week prior to the experimental protocols. Then, the animals were assigned to three experimental groups: 1) 10 Hz + PTZ (n=3); 2) 5 Hz + PTZ (n=7); and 3) 5 Hz (n=7). The stimulation consisted of a 30 min train of biphasic square-wave pulses at a current of 150 {micro}A and a pulse duration of 1 ms. Rats were subjected to the experimental protocol every 24 h for seven consecutive days. ResultsSubjects exposed to the 10 Hz died after the first PTZ injection. The 5 Hz stimulation not only prevented the animals death, but also induced a protective effect against generalization. Surprisingly, in both 5 Hz groups, septal and hippocampal spike-wave-like discharges were detected (mainly integrated by theta oscillations). This phenomenon was correlated with the generalization avoidance. ConclusionsWhile this study is preclinical in nature, our findings underscore the potential of using low-frequency medial septum stimulation for future clinical applications. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/720729v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@53482org.highwire.dtl.DTLVardef@1ba5d7corg.highwire.dtl.DTLVardef@4f999aorg.highwire.dtl.DTLVardef@1ed6744_HPS_FORMAT_FIGEXP M_FIG C_FIG

Stress is a commonly reported seizure precipitant and may contribute to the development of psychiatric comorbidities in epilepsy, yet how chronic stress interacts with epileptic circuits remains poorly understood. We investigated the impact of chronic restraint stress on physiological, behavioral, and synaptic outcomes in a mouse model of Dravet syndrome, specifically corticotropin-releasing factor (CRF) neurons in the bed nucleus of the stria terminalis (BNST), a stress-responsive region implicated in epilepsy patients. Chronic restraint stress produced divergent hypothalamic-pituitary-adrenal axis responses, with stressed Dravet syndrome mice exhibiting elevated corticosterone, increased mortality in females, and increased locomotion and anxiety-like behavior. Ex vivo electrophysiological recordings revealed that chronic stress increased spontaneous excitatory event frequency onto BNST CRF neurons in both genotypes and selectively increased sEPSC and sIPSC amplitude in Dravet syndrome mice. Evoked recordings demonstrated genotype-specific effects of stress on glutamatergic transmission in CRF neurons of the DS group. This suggests greater stress-dependent remodeling of spontaneous and evoked synaptic activity in DS. These findings suggest chronic stress may worsen physiological and behavioral outcomes in Dravet syndrome and promote specific maladaptive alterations in BNST CRF circuitry. More broadly, these results suggest that stress interacts with seizure vulnerability and potentially contributes to neuropsychiatric comorbidities and epilepsy.

The aim of this work is to validate patient-specific EEG baseline establishment using the e-norms method as a screening and retrospective-review tool for seizure detection in pediatric epilepsy. The method was applied to 247 seizure-free EEG recordings (263.92 hours) from 10 patients in the CHB-MIT Scalp EEG Database (ages 3-18). A composite stability metric combining first-derivative dynamics, spectral entropy, variance, and line length was computed per 2-second epoch across 23 channels. Patient-specific detection thresholds were derived from each patient's seizure-free baseline using a weighted statistical procedure. Performance was validated against 72 expert-annotated seizures (2,705 epochs) across 62 seizure files, with durations spanning 6 to 264 seconds (44-fold range). The results show that detection achieved 94.4% event-level sensitivity (68 of 72 seizures; 95% CI 86.6-97.8%) and 81.5% epoch-level sensitivity (2,204 of 2,705 epochs; 95% CI 80.0-82.9%). Eight of ten patients achieved 100% event-level sensitivity with epoch-level sensitivity ranging from 58.7% to 100.0%. Two patients showed partial event-level failures (CHB-15: 17 of 20; CHB-18: 5 of 6), with the four missed events attributable to two characterizable failure modes. Patient-specific thresholds ranged from 4.06 to 4.81 (mean 4.51 +/- 0.25); threshold variation did not correlate reliably with age or sex, confirming that no universal threshold could achieve comparable performance. Detection margins ranged from 0.88 to 1.24 times. Patient-specific e-norms achieves 94.4% event-level sensitivity for pediatric EEG seizure detection without requiring labeled seizure training data, exceeding published human expert inter-rater agreement (50-76%) and recent automated approaches in adult cohorts using behind-the-ear EEG and wearable ECG. Two characterizable failure modes account for the four missed events and inform appropriate clinical use. As a high-sensitivity screening tool complementary to real-time alarm systems, the method is ready for adult validation, prospective deployment, and head-to-head benchmarking.

Background and Objectives: Stereoelectroencephalography (SEEG) involves the implantation of intracerebral electrodes to investigate drug-resistant epilepsy. SEEG requires millimetric accuracy to ensure safety and optimal mapping. Although studies have evaluated SEEG accuracy, there is substantial variability in reporting. Here we report on implantation accuracy in a large series using the most common accuracy metrics described in the literature and perform a detailed analysis of contributing factors. Methods: SEEG implantations between 2013 and 2025 were included. Application accuracy was computed for each implanted electrode. Specifically, Euclidean, radial, depth, and angle error were calculated at both target and entry points. Correlative and multivariable analyses were conducted between each variable and error metric. Trajectories were also grouped by atlas-derived lobar target. Results: No metrics met assumptions of normality and thus we report accuracy using median with interquartile range (IQR). In a series of 3176 trajectories, median Euclidean target and entry errors were lower for robot-assisted electrodes (n=2858) at 2.19 (IQR: 1.54-2.98) mm and 1.38 (IQR: 0.89-2.01) mm respectively, compared to frame-based (n=318, p<.001) at 2.76 (IQR:1.79-3.76) mm and 2.21 (IQR: 1.42-3.32) mm. Correlation and multivariable regression analysis showed target error was positively correlated with implantation angle, scalp thickness, skull thickness, and trajectory length. Target error was also higher in obese patients. On lobar analysis, parietal lobe trajectories were the most accurate and frontal lobe trajectories were the least accurate. On temporal lobe trajectory analysis, posterior hippocampus trajectories were the most accurate and temporal pole trajectories were the least accurate. Presence of mesial temporal sclerosis also impacted accuracy. Conclusions: We present a detailed description of SEEG implantation accuracy, demonstrating the superior accuracy and speed of robot-assisted to frame-based methods. Furthermore, we analyzed how accuracy varies with specific factors from a global to trajectory level, which can be accounted for when planning SEEG implantations.

Objective: Pediatric epilepsy patients undergoing stereo-electroencephalography (sEEG) for ictal onset evaluation provide a rare window to study the developing brain. While methodological frameworks for task-based sEEG research are well-established in adults, pediatric-specific guidance remains underdeveloped. Furthermore, many pediatric epilepsy patients have comorbidities that might typically exclude them from participating in research. We examine factors that influence research participation and discuss considerations for conducting sEEG research in children. Methods: Here, we present a retrospective analysis of task-based research participation patterns from an NIH-funded study of speech and language representations (1R01DC018579) in 66 patients (ages 4-24) undergoing sEEG monitoring at Texas Children's Hospital to determine whether specific comorbidities influenced research participation. Results: Eighty-nine percent (n=66) of patients approached for consent agreed to participate in the study. Despite high rates of comorbidities including neurocognitive disorder (66.67%), language delay (31.75%), global developmental delay (23.81%), mood disorders (33.33%), ADHD (46.03%), autism spectrum disorder (14.29%) or other cognitive/intellectual disabilities (36.51%), all participants engaged in at least one task. While the majority of these diagnoses did not appear to influence subject participation, global developmental delay was associated with a significant reduction in time spent on active tasks. Discussion: Despite high prevalence of neuropsychological comorbidities among participants, our evidence suggests that these participants contribute meaningfully to studies investigating important developmental questions. We suggest strategies for tailoring task-based research to accommodate the unique needs of individuals in this population. Such practices are important for ensuring that research studies reflect the true diversity of the population.

Abstract Importance: Drug-resistant focal epilepsy affects approximately 30% of children with epilepsy and carries excess mortality, impaired neurodevelopment, and substantial costs. Epilepsy surgery is underutilized despite proven superiority over medical management. MRI-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive alternative to open resection, but comparative evidence to guide procedure selection is limited. Objective: To estimate lifetime outcomes and costs of epilepsy surgery versus medical management for pediatric drug-resistant focal epilepsy, and to provide etiology-informed guidance for choosing between open resection and MRgLITT. Design: Markov decision analytic model with a lifetime horizon, parameterized from published systematic reviews, meta-analyses, and cohort studies. Setting: United States, healthcare payer perspective. Participants: Hypothetical cohort of 10-year-old children with drug-resistant focal epilepsy and a seizure focus <3 cm3. Interventions: Best medical management, open resective surgery, or MRgLITT. Main Outcomes and Measures: Quality-adjusted life years (QALYs), lifetime direct medical costs, incremental cost-effectiveness ratios, and lifetime survival. Seizure outcomes were classified as seizure freedom or disabling seizures. Cost-effectiveness was assessed at $100,000/QALY. Results: Both surgical strategies were associated with a 4.6-year survival advantage, 3.6 additional lifetime QALYs, and lower costs than medical management. MRgLITT yielded 22.64 QALYs at $120,943; open resection yielded 22.62 QALYs at $121,650; medical management yielded 19.00 QALYs at $127,471. The difference between MRgLITT and open resection was 0.015 QALYs, reflecting near-equivalent effectiveness; in probabilistic sensitivity analysis, MRgLITT was optimal in 50.3% of iterations and open resection in 38.3%, with neither showing clear superiority. Etiology-specific analyses favored MRgLITT for focal cortical dysplasia and mesial temporal sclerosis, and open resection for tumor-related and cavernoma-related epilepsy. Conclusions and Relevance: Both open resection and MRgLITT were associated with substantially better lifetime outcomes and lower costs than medical management, supporting early surgical referral. Overall effectiveness between surgical approaches was clinically similar, with neither demonstrating clear superiority; the model suggests epilepsy etiology, rather than expected effectiveness alone, should guide procedure selection between MRgLITT and open resection.

Background To build a clinically translatable neonatal seizure detection algorithm using amplitude-integrated electroencephalography (aEEG) and compressed spectral array (CSA). Methods Using a public dataset of annotated neonatal EEGs, features of the aEEG and CSA were extracted from the left and right centroparietal electrodes. These features were then used to train and test three machine learning classifiers, Random Forest (RF), Support Vector Machines (SVM), and Artificial Neural Networks (ANN). Results The trained RF, SVM, and ANN classifiers had areas under the curve (AUC) of 0.80, 0.69, and 0.79 for capturing seizure time periods and an average accuracy of 0.91, 0.90, and 0.92 respectively for capturing seizure and non-seizure time periods. Median accuracy scores were higher among patients without hypoxic-ischemic encephalopathy (HIE; median = 1 for all three classifiers) than HIE patients (median = 0.92, 0.93, 0.93). Conclusion A clinically interpretable aEEG-CSA algorithm is feasible for neonatal seizure detection by extracting standard EEG features and coupling these features with a supervised ML classifier.