Epilepsy Research

Objective: To determine whether paradoxical relief, feeling unusually better after a seizure compared to before it, is more common after functional/dissociative seizures (FDS) than epileptic seizures (ES), quantify its diagnostic accuracy, and explore its relationship with preictal symptoms. Methods: Consecutive patients admitted to a tertiary epilepsy unit for prolonged inpatient EEG monitoring underwent a structured clinical interview on admission, before final multidisciplinary diagnostic classification. Preictal dissociative and autonomic/somatic symptom burden was assessed using items adapted from established questionnaires. Diagnostic classification incorporated clinical history, seizure semiology, video electroencephalography findings, and collateral information. Patients with dual or indeterminate diagnoses were excluded. Associations with paradoxical relief were examined using logistic regression, followed by an exploratory mediation analysis. Results: Of 176 patients assessed, 66 with FDS and 65 with ES were included. Paradoxical relief was reported by 46/66 patients with FDS (69.7%) and 10/65 with ES (15.4%; unadjusted odds ratio [OR] 12.65, 95% confidence interval [CI] 5.57 to 31.09). As a diagnostic signal for FDS, paradoxical relief had 69.7% sensitivity (95% CI 57.1 to 80.4), 84.6% specificity (95% CI 73.5 to 92.4), a positive likelihood ratio of 4.53 (2.51 to 8.19), and a negative likelihood ratio of 0.36 (0.24 to 0.52). FDS diagnosis remained independently associated with paradoxical relief after adjustment (OR 10.59, 95% CI 3.42 to 38.06). In a parallel mediation analysis, dissociative symptom burden showed a significant indirect effect, accounting for 19.5% of the association between diagnostic group and relief, whereas the indirect effect through somatic/autonomic symptom burden was not significant. Significance: Paradoxical relief is substantially more common after FDS than ES and may provide a simple, clinically useful diagnostic signal. Its absence does not exclude FDS, and the finding requires external validation. The association with dissociative symptoms is exploratory and supports prospective investigation of whether relief reflects transient resolution of a disturbed, disembodied preictal state.

Objective: Cognitive impairment is a common comorbidity among people with epilepsy (PWE) and is associated with disability and reduced quality of life. We characterized the burden of cognitive impairment and identified factors associated with cognitive performance in a large, population-based cohort of PWE living in Northern Peru, a region highly endemic for Taenia solium where neurocysticercosis (NCC) is a common cause of acquired epilepsy. Methods: PWE enrolled in a population-based cohort in Northern Peru between 2007 and 2020 completed the Mini-Mental State Examination (MMSE) at enrollment. Cognitive impairment was defined as an MMSE score <24. Demographic and clinical data, including epilepsy characteristics and NCC status, were collected. Negative binomial regression was used to identify factors associated with the number of MMSE errors. Results: Among 764 participants, the mean MMSE score was 26.4 (SD 4.2), and 16.4% met criteria for cognitive impairment. Memory and attention were the most affected domains. In multivariable analysis, older age and lower educational attainment were independently associated with poorer cognitive performance. Conclusion: In this large, community-based cohort from Northern Peru, approximately 1 in 6 PWE had abnormal global cognition on the MMSE, with memory and attention most affected. These findings underscore the importance of incorporating cognitive evaluation and management into comprehensive epilepsy care, particularly in resource-limited settings where cognitive morbidity may be underrecognized. Given the potential for cognitive difficulties to compound disability and adversely affect quality of life, identifying and addressing cognitive morbidity may be especially important in populations already facing substantial barriers to epilepsy care.

Background: Temporal lobe epilepsy surgery (TLS) is an effective treatment for drug-resistant focal epilepsy but is often associated with cognitive decline. A key unresolved question is how to distinguish average from severe memory loss and how these levels differentially affect everyday life. We addressed this question applying patient-derived norms of memory decline and conducting qualitative inter-views with patients experiencing expected or unexpectedly severe memory loss. Methods: Regression-based normative change criteria for postoperative verbal memory loss were derived from a single-center cohort of 806 patients. Two matched groups of four patients each were selected from the severe memory de-cline (SMD; below the 5th percentile) and average memory decline (AMD; 20th - 75th percentile) ranges. In-depth, semi-structured narrative interviews were analyzed using qualitative content analysis with a combined deductive-inductive ap-proach. Results: AMD narratives emphasized recovery, with surgery integrated into a con-tinuing sense of self. In contrast, SMD descriptions focused on persistent symp-toms, continued treatment, and illness despite meaningful seizure reduction. Pa-tients with SMD also reported limited information, insufficient psychological preparation or postoperative cognitive rehabilitation. Conclusions: Whereas AMD was generally manageable and successfully integrat-ed into everyday life, SMD disrupted identity, autonomy, and expected life trajecto-ries. Current surgical pathways appear to address these cognitive sequelae insufficiently. Improved expectation management, together with structured preoperative counseling and postoperative rehabilitation, may facilitate adaption to memory de-cline and improve long-term functioning and quality of life after surgery.

Significance: There is potential for generative artificial intelligence (AI) to perform "full stack" academic publishing, including comprehensive manuscript fabrication, "peer"-review, and editorial decision making. This study evaluated the benefits and cautions in using AI for full stack academic publishing in clinical research about seizures. Methods: Three epileptologists each selected 1 published manuscript in Epilepsia and produced an AI-fabricated manuscript about seizures. AI tools were then used to perform "peer"-review and make editorial decisions with minimal human supervision. The rates of identifying AI-fabricated manuscripts and editorial decisions among the epileptologists was analyzed, and epileptologists' observations on how AI differed from typical human "peer"-review and editorial decisions was collected. Results: Four of 6 (67%) pairs of AI-fabricated and human-generated manuscripts were correctly identified. Only 1 AI-fabricated manuscript was editorially rejected, whereas another had a subtle indicator of fabrication. When compared to human content, AI generated content was comprehensive, detailed, and based on the highest standard of academic publication. However, generated content was more verbose, used more structured responses, and more critical feedback. Conclusions: These results demonstrate that the quality of AI-fabricated manuscripts about clinical research in seizures was sufficiently high that the current methods of peer and editorial review could not easily distinguish fabricated content compared to human-written content. Moreover, AI review and editorial decisions were high quality and appeared reasonable in many cases. AI tools have matured to the point that there should be thoughtful policies that permit AI assistance but prohibit insufficiently supervised autonomous scientific submissions, reviews, and editorial decisions.

Abstract: Objective: Post-traumatic epilepsy (PTE) is a common sequela of traumatic brain injury (TBI). Research indicates that individuals with PTE tend to experience greater cognitive difficulties compared to those with TBI alone. However, it is plausible that a distinct cognitive profile exists that distinguishes between TBI cases with and without PTE. We aimed to identify longitudinal changes in cognitive measures among TBI patients to better assess the changes associated with developing PTE. Setting: Outpatient. Participants: Prospective subjects who had suffered TBI within 6 months post-injury (TBI-6M, n=32), retrospective subjects with pre-existing PTE diagnoses (PTE, n=20), and healthy control subjects (HC, n=41). Design: We examined cognitive performance for TBI patients within 6 months post-injury, then again within 12 months (TBI-12M, n=26), and within 18-months (TBI-18M, n=25), and compared this with cognitive performance among HC and PTE. Main Measures: Cognitive tests administered yielded 15 test components for analysis. We utilized linear mixed effects modeling to examine cohort-level differences cognitive function. Results: 11/15 tests showed a significant performance deficit in the PTE subjects compared to HC. TBI-6M was not significantly different from the PTE subjects; with time, 9/15 tests showed some degree of recovery in TBI subjects. Tests for information processing speed/working memory and executive function showed strong recovery (TBI-6M vs. TBI-18M, SDMT written: p<0.0001, SDMT oral and COWAT: p<0.001). Tests for visual attention/working memory also showed a smaller but significant recovery (TBI-18M vs. PTE, p<0.05). By contrast, tests for verbal memory [HVLT-R Delayed Recall] showed chronic impairment in TBI (TBI-18M vs HC, p<0.0001). TBI subjects generally trend towards recovery in cognitive performance post-TBI. Conclusions: Information processing speed/working memory are strong indicators for TBI recovery, while auditory learning/memory shows chronic impairment. The stagnation of recovery in cognitive domains typically characterized by robust recovery may correlate with an elevated risk of developing PTE.

BackgroundSerotonergic signaling plays an important role in the modulation of absence seizures (ASs), and activation of serotonin 2A receptors (5-HT2ARs) with TCB-2 suppresses spontaneous absence seizures (ASs) in Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Lisuride is a pharmacologically complex serotonergic and dopaminergic ligand with low 5-HT2AR signaling efficacy and a receptor profile distinct from that of TCB-2. We therefore investigated its effects on spontaneous ASs and the contribution of 5-HT2ARs to its actions. MethodsThe effects of systemic lisuride (0.1 and 0.5 mg/kg) on spontaneous ASs were examined in freely moving GAERS over 120 min by quantifying time spent in seizure, mean seizure duration and seizure number. The contribution of 5-HT2ARs was investigated by administering lisuride (0.5 mg/kg) following pretreatment with the selective 5-HT2AR antagonist MDL11,939 (0.5 mg/kg). ResultsLisuride produced marked dose- and time-dependent effects on ASs. At 0.1 mg/kg, lisuride elicited modest pro-absence effect. In contrast, 0.5 mg/kg produced a pronounced biphasic response, with a marked reduction in seizure activity during the first 40 min, followed by rebound increase during the second hour. The early suppression involved reductions in both seizure number and duration, whereas the delayed pro-absence effect was predominantly associated with prolonged ASs. MDL11,939 did not prevent the early seizure suppression but blocked the increase in seizure duration while producing a transient increase in seizure number. ConclusionsLisuride is a dose- and time-dependent bidirectional modulator of ASs in GAERS. The persistence of the profound early anti-absence effect during 5-HT2AR blockade indicates that this response does not require 5-HT2AR activation, whereas the modification of the delayed response by MDL11,939 supports a 5-HT2AR-dependent component in the later phase. These findings distinguish lisuride pharmacologically from TCB-2 and suggest that its biphasic effects arise from the dynamic engagement of multiple receptor mechanisms, potentially including dopaminergic signaling.

Objective: The original goal was to map neuronal circuits activated by spontaneous seizures in models of temporal lobe epilepsy. Studies used the c-fos driven TRAP2 system, which has been used successfully to label neurons after seizures. Unexpectedly, astrocytes were also labeled, then shown to express c-fos in a sustained manner after seizures. The role of these so-called fostrocytes in spontaneous seizures was studied using novel Cre-dependent AAVs. Methods: Studies used a homozygous mouse line produced by crossing TRAP2 Cre-driver mice with the Ai9 Cre-reporter line. Seizures were induced using electrical stimulation, kainic acid, or pilocarpine. Cre-dependent AAVs used the GFAP promoter to drive expression of either the catalytic A chain of diphtheria toxin (DTA), GFP, or empty vector. Spontaneous seizures were continuously recorded using EEG. Results: Discrete seizures in naive mice evoked transient c-fos expression in all astrocytes, while status epilepticus evoked a higher and sustained level of c-fos expression. Timing the activation of the TRAP2 system allowed specific labeling of the subset of astrocytes with high c-fos expression. These cells were colocalized with established astrocyte markers, showed reactive astrocyte morphology, and were selectively labeled by GFAP-driven Cre-dependent AAVs. Ablation of fostrocytes in spontaneously seizing mice increased seizure frequency. Significance: Next-generation sequencing studies have revealed a great diversity of astrocyte subtypes, identifying clusters with up-regulated c-fos expression in patients with neurological disorders. In conclusion, these studies suggest that therapies that augment the activity of c-fos expressing astrocytes would have anti-seizure activity.

Background: On-call clinicians frequently report the anecdotal impression of 'theme shifts' during which specific acute neurological diagnoses appear to cluster. Whether such clustering reflects a statistically true and reproducible phenomenon has not been systematically investigated; the present paper examines seasonality and temporal clustering within six different acute neurological conditions. Methods: In this retrospective, single-center cohort study, we identified all patients admitted to a tertiary neurological department between July 2016 and June 2026 with acute unilateral vestibulopathy, cerebral artery dissection, generalized epileptic seizures, primary intracerebral hemorrhage, peripheral facial nerve palsy, or transient global amnesia (TGA) (n = 2,140). Monthly and seasonal distributions were assessed using chi-squared goodness-of-fit and cosinor analysis. Short-term temporal clustering was tested by Monte Carlo permutation across time windows from 24 hours to 90 days, and endogenous cluster dynamics were characterized using Hawkes self-exciting point process modeling. Results: Admissions for generalized epileptic seizures showed a statistically significant deviation from a uniform monthly distribution with a winter distribution (p<0.001 and q = 0.002), and a significant temporal clustering across time windows from 72 hours to 90 days (all q < 0.05). Peripheral facial nerve palsy presented significant clustering at the 90-day window (q = 0.029) and TGA at 60-day time window (q = 0.041) without seasonality; the diagnostic groups of acute unilateral vestibulopathy, cerebral artery dissection and primary intracerebral hemorrhage showed neither seasonality nor clustering after correction for multiple comparison. No diagnostic group showed clustering within a 24-hour window, statistically significant self-excitation in Hawkes process modelling, or a significant linear trend in monthly case counts over the study period. Conclusion: The anecdotal impression of diagnostic 'theme shifts' among on-call neurologists appears to have a measurable basis, although clustering is confined to specific conditions and rather on a time scale of weeks to months. Generalized epileptic seizures were the only diagnostic group that uniquely combined seasonality with temporal clustering, suggesting a shared trigger, while facial palsy and TGA showed episodic, yet non-seasonal clustering.

Background and Objective: To compare clinical features of valproate (VPA)-induced hyperammonemic encephalopathy and asymptomatic hyperammonemia to inform monitoring strategies. Methods: This cross-sectional study at Affiliated Hospital of Jiangsu University included 25 adults with epilepsy hospitalized between January 2024 and March 2026 with serum ammonia >33 umol/L during VPA therapy. Nine met predefined VPA-induced hyperammonemic encephalopathy (VHE) criteria; 16 had asymptomatic hyperammonemia. Clinical, laboratory, electroencephalography (EEG), and neuroimaging parameters were compared. Results: VHE patients had higher ammonia (median 76.0 [IQR 51.2-155.7] vs 42.5 [33.5-66.0] umol/L; P<0.001) and shorter VPA duration (median 0 [0-60] vs 30 [0-120] months; P=0.005) than asymptomatic patients. Crucially, VPA trough concentrations and liver enzymes did not differ between groups. Diffuse EEG slowing occurred exclusively in VHE patients(66.7% vs 0%; P<0.001); prior cerebral infarction was more frequent in VHE (88.9% vs 43.8%; P=0.040). All VHE patients improved clinically within 1-3 days and achieved ammonia normalization within 3-10 days after VPA withdrawal without specific ammonia-lowering therapy. Conclusions: VHE typically emerges early in VPA therapy, is unpredictable by routine therapeutic drug monitoring or liver function tests, and resolves rapidly upon discontinuation. Clinicians should maintain a low threshold for ammonia testing in patients with new neurological symptoms during early VPA treatment, particularly those with prior cerebrovascular disease or diffuse EEG slowing. These findings support integrating ammonia screening into VPA safety protocols beyond standard therapeutic drug monitoring.

Objective To estimate the prevalence of epilepsy-associated malformations of cortical development (MCDs) in Eastern Denmark, and to validate whether epilepsy prevalence in the same population is consistent with national estimates. Methods A retrospective cohort study of people registered with ICD-10 code DG40* and/or DZ033A from 1998 up to 1 July 2023 was conducted. The study population was defined as all living residents in Eastern Denmark with at least one recorded hospital-patient contact within the year preceding 1 July 2023. Magnetic resonance imaging (MRI) availability was required to assess presence of any MCD. MRI radiology reports were manually reviewed or evaluated using a language model to identify MCDs, including encephalocele, focal cortical dysplasia (FCD), hemimegalencephaly, heterotopia, hypothalamic hamartoma, lissencephaly, polymicrogyria and schizencephaly. Prevalence estimates were calculated for each MCD subtype and for epilepsy overall, and compared with the available literature. Results On 1 July 2023, 28,739 people met inclusion criteria, and 14,434 had an available brain MRI, including radiological description of possible MCDs. The prevalence per 100,000 population was 1044.6 (95\% CI 1032.6 to 1056.6) for epilepsy and 32.1 (95\% CI 30.1 to 34.3) for any MCD associated with seizures. Reported MCD prevalence in the literature, when existent, was derived from pediatric age-ranged selected cohorts, except for FCD. No prevalence estimates for hemimegalencephaly and heterotopia were identified. Signifiance We presented the first population-based estimates of seizure-associated MCD prevalence in a large all-age cohort. Direct comparison with prior literature was prevented due to differences in study design and population structure, but epilepsy prevalence was consistent with previously reported national estimates.

Deletion of the microtubule-associated protein, tau reduces seizure burden in rodent models of genetic epilepsies and suppresses evoked seizures. In the intrahippocampal kainate (IHK) model of acquired temporal lobe epilepsy (TLE), mice lacking tau expression develop spontaneous seizures, but at a lower rate than controls. Mechanisms by which tau deletion modifies the development of acquired TLE are not well understood, but a modification of the synaptic reorganization that accompanies epileptogenesis may contribute to modified seizure expression. Increased inhibitory synaptic input to dorsal dentate granule cells (DGCs) contralateral to the focal kainate injection results after development of TLE in tau-/- mice, but inhibitory synaptic reorganization distal to the kainate lesion is undefined in this model. We therefore investigated how development of TLE modifies excitability and synaptic transmission in DGCs of the ventral dentate gyrus, distant from the kainate lesion. Our results show that development of TLE increases evoked action potential firing of ventral DGCs (vDGCs) in mice that develop TLE, demonstrating an effect of TLE development on excitability of DGCs distant from the focal injury. After development of TLE, DGCs from tau-/- mice received increased inhibitory synaptic input bilaterally, suggesting that tau expression suppresses inhibitory synaptic reorganization in DGCs. Optogenetic stimulation of interneurons in tau-/- mice revealed increased inhibitory synaptic input to vDGCs and an increase in inhibitory convergence onto vDGCs once epileptogenesis occurred. Therefore, tau deletion modifies spontaneous seizure expression after epileptogenesis in mice, potentially involving increased synaptic inhibition of DGCs throughout the dentate gyrus.

Epilepsy is increasingly recognized as a disorder involving both neuronal and vascular dysfunction. While connexin signaling has been implicated in epileptogenesis, the contribution of vascular connexins to seizure associated cerebrovascular pathology remains poorly understood. Connexin40 (Cx40) is an endothelial gap junction protein that plays a crucial role in vascular communication and blood-flow regulation. Seizures induce dynamic changes in cerebral perfusion and oxygenation, including prolonged postictal hypoperfusion/hypoxia. To determine whether Cx40 influences postictal hypoxia following focal seizures, we examined seizure characteristics and postictal oxygen dynamics in Cx40 knockout (Cx40-/-) mice using an established focal hippocampal seizure model. Electrically kindled seizures were elicited in wild-type and Cx40-/- mice, and local hippocampal tissue oxygenation was continuously monitored before and after seizure induction. Seizure duration did not differ between genotypes, indicating comparable seizure severity. Interestingly, Cx40 deletion altered the temporal pattern of postictal oxygen recovery, producing greater early hypoxia and a delayed secondary rebound in pO2 despite similar peak oxygen levels and overall hypoxic burden. These findings demonstrate that loss of Cx40 selectively alters the temporal profile of postictal oxygen dynamics without affecting seizure duration. Taken together, the results suggest that endothelial gap junctional communication contributes to postictal vascular recovery and identify Cx40 as a potential modulator of seizure associated neurovascular dysfunction.

Intrahippocampal kainate (IHK) is a well-established mouse model of temporal lobe epilepsy, in which focal hippocampal injection of kainic acid induces excitotoxic injury followed by the development of chronic spontaneous seizures. Commercial sources of kainic acid (KA) have increasingly transitioned from naturally derived to synthetic KA, which has introduced a potential source of variability to the implementation of the IHK model. Here, we evaluated injection parameters for synthetic KA, with the goal of identifying conditions that reliably produce spontaneous seizures while minimizing mortality. We found that intrahippocampal injection of 200nL of 5mM synthetic KA resulted in low mortality compared to 50-100nL of 20mM synthetic KA (a dosing range commonly used with naturally derived KA), while robustly inducing TLE-like hippocampal sclerosis and recurrent spontaneous electroclinical seizures. We further demonstrated high inter-animal variability in both seizure frequency and temporal clustering of seizures across animals receiving either injection protocol (200nL of 5mM or 50nL of 20mM). Together, these findings provide a framework for implementing the IHK model with synthetic KA and support its continued use to advance our understanding of the cellular and network mechanisms underlying temporal lobe epilepsy.

Based on the observation that in normal EEG rhythms, the low-voltage beta frequencies dominate in the anterior region while characteristic high(er)-amplitude slower rhythms manifest more posteriorly, we studied these gradients across normal subjects and patients with different monogenic epilepsies. From large data sets (long term records of 374 controls and 241 patients) we selected 60s eyes-open rest-EEG epochs to determine the spectral power of the EEG bands. To help manage the large data sets and facilitate analyses, we employed AI to preselect and assist in coding. While both preselection and coding was extensively verified and validated by the authors, which was a time-consuming effort, the AI contribution reduced the net effort of evaluating the large dataset. We developed a metric that reflects the anterior-posterior gradients of the beta rhythm and the so-called posterior dominant rhythm. Our results indicate that this simple gradient measure across 1-10 year-age groups may provide a robust quantitative biomarker of cerebral dysfunction in monogenic epilepsy. Because EEG is noninvasive, widely available, repeatable, and relatively inexpensive, such a biomarker could ultimately provide a practical means of assessing the cerebral effects of emerging targeted therapies across multiple genetic epilepsies.

Background and Objectives: In persons with epilepsy, seizure risk is tightly linked to the health of sleep and circadian rhythms. Rest-activity rhythms (RARs), derived from continuously worn activity monitors, can provide objective assessments of diurnal patterns of activity. Compared with healthy controls, adults with epilepsy have been shown to display weak and unstable RARs. In this study, we aimed to directly measure RARs in patients with infantile epileptic spasms syndrome (IESS), a potentially devastating developmental and epileptic encephalopathy. As a comparator, we similarly examined identically measured RARs from a cohort of healthy infants. Methods: For this cross-sectional case-control comparison, we obtained multiday actograms in a sample of infants with IESS using ankle-worn Actiwatch-2 devices deployed during overnight follow-up EEG evaluations designed to assess initial treatment efficacy. Control actograms (similarly obtained via Actiwatch-2 devices) from the Rise & SHINE study (Sleep Health in Infancy and Early Childhood) were downloaded from the National Sleep Research Resource. We computed a series of parametric and non-parametric measures to depict the maturation of RARs over this developmental window and compared RARs from each IESS subject against up to 4 age-matched controls. Results: In 891 actigraphy recordings obtained from 333 SHINE subjects, age-dependent increases in body length and weight were associated with progressive increases in RAR height (amplitude/mesor/M10), regularity (interdaily stability), entropy and fractal complexity, together with progressive declines in RAR fragmentation (intradaily variability). Compared with age-matched controls, multiday actograms from IESS subjects (n = 11, 9 males) displayed marked reductions in RAR height (amplitude/mesor/M10) and interdaily stability, together with reductions in entropy and fractal complexity. Conclusions: During infancy, rest-activity rhythms display a stereotyped maturation in height, complexity and day to day consistency, revealing a developmental "growth curve" of RAR maturation. Severe RAR disruptions in infants with IESS may relate to the encephalopathy imposed by the underlying genetic/metabolic condition, structural lesion, and/or the psychomotor retardation imparted by antiseizure medications. Actigraphy recordings may offer a scalable, noninvasive approach to objectively and longitudinally assess circadian health in patients with IESS.

ObjectiveThe current International League Against Epilepsy (ILAE) guidelines for Lennox-Gastaut syndrome (LGS) mandate the presence of generalized paroxysmal fast activity (GPFA) on EEG. However, GPFA is not necessarily restricted to LGS and has been described in, among others, idiopathic generalized epilepsies. A clear definition for GPFA is currently lacking, hampering research into its utility as a diagnostic or treatment biomarker. Here, we assessed expert agreement in the interpretation of GPFA to explore feasibility of a consensus-based definition. MethodsWe internationally distributed a two-part survey on GPFA to EEG experts. First, participants completed thirteen questions gauging their preferred clinical and EEG criteria for GPFA, including duration, frequency, amplitude and topography. Second, participants classified the presence versus absence of GPFA in eleven EEG clips, while blinded to clinical context, from patients with LGS, other epilepsies, and physiological variants. Results162 respondents, predominantly from North America and Europe, completed the survey. 87% considered GPFA to also occur in epilepsies other than LGS. Considerable heterogeneity was present on defining duration, spectral frequency, amplitude and topographic distribution of GPFA. Particularly poor agreement was seen for lower limits of duration and frequency, with no single response option receiving a majority consensus (36% and 30% agreement, respectively). Similarly, the degree of agreement on interpretations was highly variable across real-world EEG clips. SignificanceMarked discrepancies exist in the EEG identification and clinical interpretation of GPFA, undermining its utility as a potential biomarker in research and clinical trials of LGS and other epilepsies. The findings also highlight the need to establish a consensus-based and eventually evidence-informed definition to formally operationalize the clinical and EEG criteria for GPFA. Key pointsO_LIGeneralized paroxysmal fast activity (GPFA) is variably defined in the literature, limiting its utility as a diagnostic or treatment biomarker C_LIO_LIIn this international survey (n = 162 respondents, 25 countries) we found limited agreement on GPFAs defining features and on interpretation of fast activity on EEG clips C_LIO_LI87% of respondents considered GPFA to occur in epilepsies other than Lennox-Gastaut syndrome C_LIO_LIPending further elucidation of the pathophysiology underlying GPFA or its computational characterization (i.e., to inform a biologically-or evidence-based definition), we underscore the need for an interim consensus-based definition C_LI

Introduction: Neurocysticercosis (NCC) is an infection of the central nervous system caused by the tapeworm Taenia solium. Despite documented increases of NCC in California, large-scale studies characterizing affected populations remain limited. The spectrum of NCC associated neuropsychiatric comorbidities has not been well defined in U.S. populations. This study aimed to estimate the prevalence of NCC within the University of California (UC) Health System, characterize the population demographic and clinical features, and identify factors associated with epilepsy among individuals with NCC. Methodology/Principal Findings: We conducted a cross-sectional analysis of electronic health records from 2012 through March 2026 using the UC Health Data Warehouse, which integrates data from six UC Health systems. Among individuals aged [&ge;] 1 year, there were 713 individuals with a diagnosis of NCC corresponding to a prevalence of 6.17 per 100,000. A comparison group was randomly selected at a 1:10 ratio. Relative to the comparison group, NCC patients were significantly older, more likely to identify as Hispanic or Latino, more likely to speak Spanish as a primary language, and more likely to have Medicaid insurance. NCC was strongly associated with epilepsy (OR = 19.20, 95% CI: 15.74-23.46), as well as migraines, cognitive impairment, mood disorders, Parkinsons disease, substance use, stroke, and sleep disorders. After adjusting for age, gender, and ethnicity, male NCC patients had 26% higher odds of epilepsy compared to female patients. Conclusion/Significance: In addition to epilepsy, NCC was associated with a broad range of neuropsychiatric comorbidities and occurred disproportionately among patients more likely to face socioeconomic and structural barriers to care, including limited insurance coverage, language barriers, and immigration-related challenges. These findings highlight the importance of recognizing NCC in non-endemic settings, where this often underrecognized disease contributes substantially to neurologic morbidity in a vulnerable population.

Resistance to anti-seizure medications (ASMs) remains a major clinical challenge in the management of epilepsy. Neuroinflammation has been implicated as a contributing mechanism and, consistent with this, antagonists of the ATP-gated P2X7 receptor (P2X7R) have been shown to enhance ASM efficacy in animal models. It remains unclear, however, if P2X7R antagonism is effective in human models of drug-resistant epilepsy. Here, we assessed the seizure-suppressive potential of the P2X7R antagonists AFC-5128 and JNJ-47965567 using electrophysiological recordings in acute resected brain slices from patients with epilepsy using artificial cerebrospinal fluid containing low Mg2+ and high K+ to evoked seizure-like events. P2X7R antagonists alone did not suppress seizure-like activity. When co-administered, however, P2X7R antagonists significantly enhanced the anti-seizure efficacy of carbamazepine and lorazepam. Notably, P2X7R antagonist treatment lowered Interleukin-1{beta} levels, and betaine, a drug targeting Interleukin-1{beta} release, mimicked the effects of P2X7R antagonists when combined with carbamazepine. Finally, mice with microglia-specific P2X7R depletion showed improved responsiveness to carbamazepine, suggesting P2X7R-mediated effects are partially mediated via their functions in microglia. These findings suggest that P2X7R-based therapies may represent an effective add-on approach for treating drug-resistant seizures associated with neuroinflammation.

Childhood absence epilepsy (CAE), the most common childhood epilepsy syndrome, is associated with bursts of generalized thalamocortical spike-wave discharges and cognitive impairment, yet the physiological mechanisms linking disease activity, treatment, and cognition remain unclear. Sleep spindles, generated by thalamocortical circuits, are associated with cognitive function and may be disrupted by epileptic activity. Here, we retrospectively studied 87 EEGs from 53 children with active and resolved CAE and 87 age- and sex-matched controls to evaluate sleep spindle activity across disease states and its association with antiseizure medication (ASM) exposure. We found that children with active CAE had reduced spindle rates across all cortical regions compared to those with resolved CAE and controls, with the largest reduction in the frontal region, where epileptic spike activity was also most prominent. Spindle rate was inversely correlated with epileptic spike rate, consistent with a shared thalamocortical circuitry. The association between ASM exposure and spindle rate varied by disease state. In active CAE, treated children had higher spindle rates than untreated children. In resolved CAE, treated children had lower spindle rates than untreated children. In contrast, ASM-related differences in spike rate were more limited, although a medication-specific reduction was observed in active CAE. These findings support sleep spindle rate as a candidate physiological marker of disease state and ASM exposure in children with CAE. Given the established role of sleep spindles in memory consolidation, these findings support testing of whether spindle disruption provides a mechanistic link between epileptic thalamocortical activity and cognitive vulnerability in CAE.

Objective: Whether a scheduled antiseizure medication (ASM) continues on schedule across the ICU-to-floor transfer has not been characterized. We quantified ASM administration-gap frequency across this transfer and compared it with gap frequency during matched non-transfer intervals in the same patient and drug. Methods: In this retrospective MIMIC-IV (version 3.1) cohort study, we identified epilepsy and status-epilepticus admissions with an ICU stay followed by floor transfer and a scheduled ASM order active at ICU departure. A gap was defined as an interval exceeding 1.5 times the expected dosing interval between the last ICU dose and first floor dose, or no further dose before discharge, and compared with a matched non-transfer control interval in the same patient and drug (paired McNemar test). A multivariable model evaluated six prespecified clinical predictors; sociodemographic variables were summarized descriptively. Results: Among 2,469 ASM transition-by-drug observations (1,583 admissions, 1,335 patients), an administration gap occurred in 251 (10.2%; 95% CI, 8.7%-11.7%). Gap frequency across the transfer exceeded frequency during matched non-transfer control intervals in the same patient and drug: a paired rate difference of 5.8 percentage points (95% CI, 4.4-7.1; 7.5% vs 1.7%; P = 7.3 x 10^-22) before the transfer and 6.4 percentage points (95% CI, 4.9-7.9; 8.9% vs 2.5%; P = 1.9 x 10^-23) after. Gap rates were similar for intravenous-available (9.9%) and oral-only (11.4%) drugs (rate difference, 1.5 percentage points; 95% CI, -1.6 to 4.5; P = .34). None of six prespecified predictors reached significance after correction. Significance: An antiseizure medication administration gap occurred in approximately 1 of every 10 drug-transition observations at the ICU-to-floor transfer, exceeding matched non-transfer gap rates by 5.8 to 6.4 percentage points. This transfer-associated excess, rather than any single medication or patient characteristic, supports a structured medication-continuity check.