Epilepsia[JOURNAL]
Sun
200 papers
Biofluid-specific variations in circulating 5' transfer RNA fragments during ictal and interictal states in experimental temporal lobe epilepsy.
Soukupova M, Morrissey EP, Guarino A … +13 more , Marino P, Pareo C, Birtolo N, Zaheer S, Stewart R, Woods I, Rosenow F, Hamer H, Körtvélyessy P, Pfeiffer S, Henshall DC, Prehn JHM, Simonato M
Epilepsia · 2026 Apr · PMID 41973185 · Publisher ↗
OBJECTIVE: Circulating small noncoding RNAs represent potential biomarkers of temporal lobe epilepsy (TLE). Recently, two transfer RNA fragments (tRFs), 5'tRF Glu-CTC and Gly-GCC, were found to be elevated in plasma samp...
OBJECTIVE: Circulating small noncoding RNAs represent potential biomarkers of temporal lobe epilepsy (TLE). Recently, two transfer RNA fragments (tRFs), 5'tRF Glu-CTC and Gly-GCC, were found to be elevated in plasma samples collected in advance of a seizure in TLE patients, suggesting they may serve as potential wet biomarkers of seizure risk or occurrence. The optimal biofluid source for tRF assay, species conservation, and whether their levels reflect specific ictal or interictal states remain uncertain. METHODS: Here, we analyzed the longitudinal dynamics of 5'tRF Glu-CTC and Gly-GCC in both cerebrospinal fluid (CSF) and plasma in the pilocarpine model of TLE in rats. We sampled CSF and plasma across multiple time points during the chronic phase of TLE, while performing continuous electroencephalographic monitoring to correlate 5'tRFs levels with electrophysiological activity. RESULTS: Levels of both 5'tRFs were significantly higher in plasma but not in CSF in epileptic rats compared to controls. Plasma levels of both did not, however, correlate with seizure frequency. In contrast, 5'tRF Gly-GCC levels in CSF correlated with interictal spike activity, whereas plasma levels again did not show a dynamic response. Consistent with these findings, we observed higher levels of 5'tRFs in plasma but not in CSF samples from human TLE patients as compared with healthy controls. SIGNIFICANCE: These data suggest that 5'tRFs accumulate in the brain during interictal spike activity and accumulate in the plasma of individuals with epilepsy. 5'tRFs may therefore serve as accessible, diagnostic biomarkers for epilepsy.
Targeted senotherapy improves electrographic and behavioral outcomes in a mouse model of temporal lobe epilepsy.
McFall DJ, Hussain AI, Cho M … +1 more , Forcelli PA
Epilepsia · 2026 Apr · PMID 41972901 · Publisher ↗
OBJECTIVE: Current pharmacotherapy for temporal lobe epilepsy (TLE) is limited to symptomatic treatment and leaves approximately one third of patients with inadequate seizure control. Discovering disease-modifying target...
OBJECTIVE: Current pharmacotherapy for temporal lobe epilepsy (TLE) is limited to symptomatic treatment and leaves approximately one third of patients with inadequate seizure control. Discovering disease-modifying targets is an unmet clinical need. We have previously identified senescent cells (SCs) as one such target. Many drugs that eliminate SCs (senolytics) interfere with apoptotic resistance proteins, potentially resulting in broad cytotoxicity and numerous side effects. Newer, more targeted therapies, like selective senescence killing compound 1 (SSK1), a gemcitabine prodrug that is selectively activated in SCs, offer the possibility to reduce off-target effects, but SSK1 has yet to be investigated in any preclinical epilepsy model. METHODS: We used pilocarpine to induce status epilepticus (SE) in 3- to 4-month-old mice. Immediately following SE, mice were randomly assigned to receive either SSK1 treatment or vehicle for the remainder of the study. We assessed behavioral performance on memory tasks, seizure burden by EEG, and histological markers of SCs. RESULTS: SE robustly increased hippocampal and thalamic expression of SC marker p16 by over 100% compared to saline controls. SSK1 treatment reduced p16+ cells by ~45%, without any apparent neurotoxicity. In addition, SSK1 treatment normalized spatial memory impairments and reduced spontaneous seizure burden, completely protecting a majority (60%) of animals from seizures. SC burden in the hippocampus, but not the thalamus, correlated with seizure burden in vehicle-treated animals. SIGNIFICANCE: These findings lend further credence to the viability of targeting SCs to treat TLE. As with other genetic and pharmacologic SC ablation strategies, SSK1 produced a similar reduction in p16+ cells and normalization of spatial memory. SSK1, however, displays a stronger protective effect against seizures. In short, SSK1 is a compelling, translationally viable option for senolysis in TLE.
Redefining the treatment pathway for medication-resistant epilepsy in the cenobamate era: Surgical obviation or surgical delay.
Kerr WT, McFarlane KN
Epilepsia · 2026 Apr · PMID 41972812 · Publisher ↗
Abstract loading — click title to view on PubMed.
Cardiac remodeling and arrhythmia in a mouse model of Depdc5 haploinsufficiency.
Ramos-Mondragon R, Wang S, Liu Q … +7 more , Chen C, Greiner AM, Marx AM, Shih M, Parent JM, London B, Isom LL
Epilepsia · 2026 Apr · PMID 41954126 · Publisher ↗
OBJECTIVE: Some ion channel genes linked to developmental and epileptic encephalopathy (DEE) are also linked to cardiac arrhythmia, leading to the hypothesis that predisposition to cardiac arrhythmias may contribute to t...
OBJECTIVE: Some ion channel genes linked to developmental and epileptic encephalopathy (DEE) are also linked to cardiac arrhythmia, leading to the hypothesis that predisposition to cardiac arrhythmias may contribute to the complex disease presentation of DEE and possibly to the mechanism of sudden unexpected death in epilepsy. However, channelopathies represent only ~25% of the genetic epilepsies. The remainder arise from variants in non-ion-channel genes, moving the disorder beyond channelopathies. Despite evidence that some non-ion-channel variants are linked to sudden cardiac death, we have little information on whether non-ion-channel DEE variants can also result in cardiac phenotypes. METHODS: Here, we investigated the DEE gene, DEPDC5, which is expressed in both brain and heart. We studied the cardiac phenotype of a Depdc5 haploinsufficient mouse model that genetically mimics DEPDC5 patients. RESULTS: Depdc5 mice showed increased susceptibility to ventricular arrhythmias, systolic dysfunction, and ventricular fibrosis, as well as shortened action potential duration, increased levels of sodium and potassium channel proteins, and increased sodium current and transient outward potassium current densities in acutely isolated ventricular myocytes. Thus, at least in mice, Depdc5 variants impact heart as well as brain excitability. SIGNIFICANCE: These data strengthen the hypothesis that cardiac arrhythmias may contribute to the complex presentation of DEE and expand our previous work showing cardiac arrhythmia in multiple mouse and human channelopathy models to include a model of a non-ion-channel variant. Although this work may have implications for DEPDC5 patients, critical differences between mouse and human cardiac physiology complicate the translation of mouse data to human disease. Essential next steps must include investigation of Depdc5 function in higher vertebrate models that more accurately mimic human physiology, as well as longitudinal patient natural history studies that monitor cardiovascular health, to test the hypothesis that DEE variants resulting in DEPDC5 haploinsufficiency may predispose patients to cardiac arrhythmias.
Association of carotid revascularization with epilepsy and seizures in patients with carotid stenosis.
Chuang MT, Chang Y, Wong CE … +2 more , Huang CY, Perng PS
Epilepsia · 2026 Apr · PMID 41948863 · Publisher ↗
OBJECTIVE: The potential influence of carotid stenosis on seizure or epilepsy outcomes and whether revascularization modifies this risk remain understudied. METHODS: Using a large real-world database, we identified adult...
OBJECTIVE: The potential influence of carotid stenosis on seizure or epilepsy outcomes and whether revascularization modifies this risk remain understudied. METHODS: Using a large real-world database, we identified adults diagnosed with carotid stenosis and excluded those with prior seizures, epilepsy, or common provoking conditions. Patients were classified according to whether they underwent carotid endarterectomy or carotid artery stenting within 1 month of diagnosis. Propensity score matching was performed based on demographic variables and major vascular comorbidities. The primary outcome was a composite of new onset seizures or epilepsy at 1 month, 3 months, and 2 years of follow-up. RESULTS: Among 848 939 eligible patients, 41 225 were matched. Carotid revascularization was associated with significantly lower risk of seizures or epilepsy. Incidence in the revascularization group was .3% at 1 month, .4% at 3 months, and .8% at 2 years, corresponding to hazard ratios of .30 (95% confidence interval [CI] = .24-.38), .36 (95% CI = .30-.43), and .41 (95% CI = .36-.47), respectively. These associations remained consistent across symptomatic and asymptomatic subgroups and between procedural modalities. In sensitivity analysis including patients who experienced ischemic or hemorrhagic stroke after carotid stenosis diagnosis, seizure or epilepsy incidence remained lower in the revascularization group, with hazard ratios of .27 (95% CI = .18-.41) at 3 months and .35 (95% CI = .28-.45) at 2 years. SIGNIFICANCE: Beyond its established role in stroke prevention, carotid revascularization was associated with reduced incidence of seizures or epilepsy in this real-world analysis. This association persisted even among patients who experienced cerebrovascular events following the procedure. The potential protective effect of revascularization and its underlying mechanisms warrant further investigation.
Charlotte Dravet: Life and contributions to epileptology.
Medina MT, Genton P
Epilepsia · 2026 Jun · PMID 41945416 · Publisher ↗
Abstract loading — click title to view on PubMed.
Sodium-glucose cotransporter 2 inhibitors and the risk of late onset epilepsy: A real-world cohort study.
Lin BH, Huang HM, Lin HA … +1 more , Lin SF
Epilepsia · 2026 Apr · PMID 41940606 · Publisher ↗
OBJECTIVE: Late onset epilepsy (LOE) is associated with substantial morbidity. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) may exert neuroprotective effects. This study evaluated the association between SGLT2i and...
OBJECTIVE: Late onset epilepsy (LOE) is associated with substantial morbidity. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) may exert neuroprotective effects. This study evaluated the association between SGLT2i and risk of LOE among older adults with type 2 diabetes mellitus. METHODS: This retrospective cohort study was conducted between 2013 and 2025 with a 3-year follow-up using the TriNetX global network. Patients ≥60 years old with type 2 diabetes mellitus were classified into two cohorts-new SGLT2i users and new dipeptidyl peptidase-4 inhibitors users-following a 6-month washout of other antihyperglycemic agents except metformin. Patients with major neurological diseases or contraindications to SGLT2i were excluded. Propensity score matching was used to balance baseline characteristics between two cohorts. The primary outcomes were incident LOE, status epilepticus, and initiation of antiseizure medications. Unadjusted Cox proportional hazards models were applied to estimate hazard ratios (HRs) and 95% confidence interval (CIs). RESULTS: A total of 1 435 648 patients were identified. After matching, 60 203 patients were included in the SGLT2i cohort (mean age = 67.7 years, 42.3% female) and 60 203 in the control cohort (mean age = 67.7 years, 41.7% female). SGLT2i use was associated with lower risk of LOE (HR = .55, 95% CI = .44-.68), status epilepticus (HR = .38, 95% CI = .21-.69), and antiseizure medication initiation (HR = .63, 95% CI = .58-.69). SGLT2i reduced LOE risk in patients with stroke (HR = .69, 95% CI = .42-.88) and dementia (HR = .44, 95% CI = .25-.78) but not in those with traumatic brain injury or brain tumors. SIGNIFICANCE: SGLT2i use was associated with reduced risk of LOE among selected patients, supporting its role in an etiology-specific therapeutic approach for older adults at risk of epilepsy.
Stereo-EEG mapping of visual working memory with task-related high-gamma modulations.
Ervin B, Buroker J, Cummins T … +11 more , Byars AW, Scholle C, Rozhkov L, Horn PS, Tenney JR, Greiner HM, Leach JL, Skoch J, Mangano FT, Holland KD, Arya R
Epilepsia · 2026 Apr · PMID 41934264 · Publisher ↗
OBJECTIVE: We describe a safe, informative, and easy-to-implement approach for presurgical mapping of visual working memory (VWM) with stereo-electroencephalography (SEEG). METHODS: Twenty-four patients with drug-resista...
OBJECTIVE: We describe a safe, informative, and easy-to-implement approach for presurgical mapping of visual working memory (VWM) with stereo-electroencephalography (SEEG). METHODS: Twenty-four patients with drug-resistant epilepsy, 11-23 years of age, performed a single-probe change detection VWM task, during SEEG monitoring. High-gamma modulations (HGMs) and connectivity modulations (weighted phase lag index) were computed for encoding, retention, recall, and response phases compared to a rest phase. Effects of lesioning sites with significant HGM on neuropsychological outcomes were analyzed. RESULTS: Validity of our VWM task was evident by picture vocabulary scores covarying positively with increasing consistency and negatively with increasing maximum latency of the response times, respectively. VWM task elicited specific patterns of cortical HGMs during each phase: bilateral frontoparietal augmentation during encoding, replaced by widespread suppression during retention, followed by diffuse bilateral augmentation during the recall and response phases. Distinct neural circuits were also observed during each phase of the VWM task: left-lateralized phonological loop during encoding, short-range bilateral frontal connectivity during retention, and interhemispheric peri-Rolandic hubs during recall and response phases. Lesioning sites with significant high-gamma augmentation was associated with declines in domains directly relevant to VWM including working memory (slope -6.18, p < .001), visuospatial (-1.17, p = .031), picture vocabulary (-1.45, p < .001), and letter-word identification (-6.39, p = .004), whereas lesioning sites with significant high-gamma suppression, particularly in recall and response phases, affected domains sharing resources for neural computations with working memory, but not directly related to VWM including processing speed (-16.04, p = .049), calculation (-19.12, p = .020), and verbal comprehension (-9.09, p = .020). SIGNIFICANCE: Our observations extend theoretical models of VWM by providing phase-specific engagement of neural subsystems, particularly of phonological loop during encoding of even visually-cued stimuli and spatial rehearsal mechanisms during retention. Clinically, adverse neuropsychological outcomes from lesioning of VWM sites during epilepsy surgery support wider adoption of VWM mapping during presurgical evaluation of patients with drug-resistant epilepsy.
Clinician knowledge gaps in epilepsy surgery: An international survey across 18 countries or regions in Asia-Oceania.
Ravat P, Fong SL, Parihar J … +14 more , Veeramuthu V, Garg S, Nakagami Y, Liang S, Peng J, Chen C, Putra MAY, Soontornpun A, Mantos KB, Le MT, Lin CY, Thakkar M, Asranna A, Kuroda N
Epilepsia · 2026 Apr · PMID 41931042 · Publisher ↗
OBJECTIVE: This study was undertaken to assess clinicians' knowledge of epilepsy surgery across Asia-Oceania and identify individual- and country- or region-level factors associated with this knowledge, to inform strateg...
OBJECTIVE: This study was undertaken to assess clinicians' knowledge of epilepsy surgery across Asia-Oceania and identify individual- and country- or region-level factors associated with this knowledge, to inform strategies addressing the epilepsy surgery treatment gap. METHODS: We conducted a multinational, cross-sectional, web-based survey of clinicians involved in epilepsy care across 18 countries or regions in Asia-Oceania (May-September 2024). The primary outcome was an epilepsy surgery knowledge score (range = 0-12), derived from 12 multiple-choice items covering indications for surgery, referral timing, understanding of surgical procedures, misconceptions about antiseizure medication efficacy, and perceived contraindications (e.g., electroencephalographic/magnetic resonance imaging findings, eloquent cortex, memory risk, psychiatric comorbidity, and intellectual disability). Linear mixed-effects models were used to identify individual-level predictors of knowledge, with country or region modeled as a random intercept. Ancillary analyses examined correlations between country- or region-level knowledge effects and academic activity related to epilepsy. RESULTS: A total of 809 clinicians were included, with respondents primarily from India (n = 204), China (n = 194), and Japan (n = 93). The mean knowledge score was 7.3 ± 2.9, with item-level correct response rates ranging from 11.2% to 87.6%. Higher knowledge was independently associated with being an epileptologist or neurosurgeon, working at a center with an epilepsy surgery program, and higher epilepsy case volume. Lower knowledge was observed among clinicians outside core neurological specialties. Significant country- or region-level variation persisted after adjustment and correlated with national academic activity in epilepsy surgery and epilepsy awareness. SIGNIFICANCE: Clinician knowledge of epilepsy surgery varies substantially across Asia-Oceania. Although targeted education is necessary, structural factors such as the availability of epilepsy surgery programs and national academic engagement also appear critical for translating knowledge into access. Multilevel strategies that integrate education with health-system strengthening are needed to meaningfully reduce the epilepsy surgery knowledge and treatment gaps.
Language mapped to a high-resolution brain atlas for surgical evaluation of epilepsy patients.
Watson EM, Collins E, Chishti O … +7 more , Bose-Roy R, McGrath H, Akierman Segal N, Lehman R, Sivaraju A, Zaveri HP, Spencer DD
Epilepsia · 2026 Apr · PMID 41931039 · Full text
OBJECTIVE: We created composite maps of language function from extraoperative stimulation literature and transformed them to the Yale Brain Atlas (YBA), which offers precise cortical localization with 690 one cm parcels,...
OBJECTIVE: We created composite maps of language function from extraoperative stimulation literature and transformed them to the Yale Brain Atlas (YBA), which offers precise cortical localization with 690 one cm parcels, based on the MNI152 template and anatomical landmarks. This allowed comparison to similarly transformed direct cortical stimulation (DCS) maps created from medically intractable epilepsy patients studied intracranially at Yale University and selected fMRI activation data. Our goal was to create anatomically precise boundaries of language function and support individualized planning for intracranial EEG (icEEG) studies and/or surgical resection. METHODS: A systematic search of DCS studies of language-related functions identified 12 stimulation studies (10 subdural, two stereo-EEG) that provided sufficiently clear surface visualizations for parcel-level mapping. Language-positive sites from six commonly tested functions (visual naming, auditory naming, naming (auditory/visual), reading, repetition and speech arrest) were manually co-registered to YBA parcels using conserved anatomical landmarks, facilitating topological comparison among similar language functions from the literature, Yale's electrical stimulation mapping cohort, and Neurosynth and Parcelsynth fMRI activation. RESULTS: Across 1182 patients, 176 YBA parcels (approximately 25% of cortical parcels) were implicated in at least one language task. Composite stimulation maps demonstrated robust consistency with the Yale DCS cohort and substantial overlap with distributed fMRI language networks. The resulting interactive maps provide parcel-level specificity while highlighting under-sampled but functionally critical regions. SIGNIFICANCE: The maps provide a review of language function determined through DCS and meta-analytic repositories of fMRI activation data. By consolidating stimulation-derived language data into a high-resolution parcellated atlas, this work offers a spatially detailed surface-based representation of language boundaries for surgical planning. The YBA facilitates standardized multimodal communication and allows patient-specific stimulation results to be interpreted within population-derived functional boundaries.
Pediatric sensorimotor cortical responsiveness to intracerebral stimulation during stereoelectroencephalographic monitoring: Age effects and area specificity.
Nobile G, Tassi L, Ponzano M … +8 more , d'Orio P, Consales A, Bosisio L, Francione S, Arnulfo G, Sormani MP, Nobili L, Mai R
Epilepsia · 2026 Apr · PMID 41931012 · Publisher ↗
OBJECTIVE: This study was undertaken to determine how age influences clinical responsiveness to intracerebral electrical stimulation (IES) in children across primary and secondary sensorimotor cortices and to assess age...
OBJECTIVE: This study was undertaken to determine how age influences clinical responsiveness to intracerebral electrical stimulation (IES) in children across primary and secondary sensorimotor cortices and to assess age effects on response complexity and area-specific responsiveness. METHODS: A retrospective cohort of pediatric (≤16 years) stereoelectroencephalographic procedures was analyzed. A total of 1750 IESs were delivered in 33 implantations (31 patients). Precentral and postcentral gyri were considered as primary areas; secondary areas included premotor cortex (PREMOT), supplementary sensorimotor area (SSMA, including presensorimotor area), anterior/central cingulate (ACC), and pre-/postcentral opercula (PREC-OP and POSTC-OP). Clinical responses were classified as simple motor, sensory, language, or undefined. Complexity was coded as integrated (one coordinated action) or multiple (signs from different domains occurring together). Mixed-effects models were adjusted for antiseizure medication load, cognitive level/neurodevelopmental delay, and stimulation frequency (1 vs. 50 Hz). Age was modeled continuously (per year) and categorically (≤9 vs. >9 years). RESULTS: Clinical response rate increased with age in the overall cohort (per-year incidence rate ratio [IRR] = 1.11, 95% confidence interval [CI] = 1.03-1.21, p = .007). Categorical modeling showed a higher rate in subjects aged >9 years (IRR = 1.89, 95% CI = 1.02-3.51, p = .044). Integrated responses did not vary with age, whereas multiple responses were more likely in older children (overall adjusted odds ratio [OR] = 3.65, 95% CI = 1.24-10.77, p = .019; without postdischarge: adjusted OR = 5.30, 95% CI = 1.38-20.36, p = .015). Using PREMOT as reference, all other regions were more responsive, forming two clusters: lower (ACC, PREC-OP/POSTC-OP) and higher (SSMA, precentral, postcentral); SSMA showed rates comparable to primary cortices. SIGNIFICANCE: Pediatric cortical responsiveness to IES rises with age and is independent of medication burden, cognitive level, and stimulation frequency. Older children also show more multidomain responses, consistent with developing large-scale integration. These results can inform age-aware stimulation mapping in clinical practice.
Glymphatic dysfunction couples with cortical excitation-inhibition imbalance in epilepsy: Evidence from Rasmussen encephalitis.
Fu C, Yang Y, Gong P … +9 more , Lv K, Liu Y, Tang C, Wang X, Cai L, Liu Q, Jiang Y, Ji T, Luan G
Epilepsia · 2026 Apr · PMID 41928687 · Publisher ↗
OBJECTIVE: The glymphatic system (GS) facilitates perivascular clearance of interstitial solutes and is modulated in part by neuronal activity. However, its relationship to cortical excitability in epilepsy remains uncle...
OBJECTIVE: The glymphatic system (GS) facilitates perivascular clearance of interstitial solutes and is modulated in part by neuronal activity. However, its relationship to cortical excitability in epilepsy remains unclear. We aim to clarify the mechanistic link between GS function and cortical excitation-inhibition (E-I) balance in patients with epilepsy. METHODS: We investigated this coupling in patients with Rasmussen encephalitis (RE), a rare epileptic disorder with unilateral cortical pathology. Using a hemispheric within-subject design (N = 20), we compared the affected hemisphere (AH) and unaffected hemisphere (UH) within each patient, assessing glymphatic function via diffusion MRI (diffusion tensor imaging-analysis along the perivascular space [DTI-ALPS] index) and E-I dynamics via resting-state EEG spectral decomposition. RESULTS: The AH exhibited reduced DTI-ALPS indices, elevated aperiodic exponents, and increased delta-theta oscillatory power. Across individuals, lower ALPS values in the AH correlated with higher aperiodic exponents (r = -.496, p = .026), but not with periodic EEG features. Principal component analysis (PCA) of channel-level aperiodic asymmetry (exponent-informed PCA) revealed a spatial pattern localized to atrophic cortical regions, which also showed strong correspondence with interhemispheric ALPS asymmetry (r = -.570, p = .009). SIGNIFICANCE: These findings demonstrate a spatially convergent link between glymphatic dysfunction, cortical activity with predominant inhibitory tone, and focal atrophy in the AH. Our results indicate that impaired perivascular clearance is correlated with altered cortical excitability, highlighting the potential role of the GS in maintaining neural stability in the epilepsy.
Expanding the longitudinal trajectory and genotypes of TBC1D24-related epilepsy.
Xiang S, Fei L, Li T
Epilepsia · 2026 Jun · PMID 41925529 · Publisher ↗
Abstract loading — click title to view on PubMed.
Transcriptional signatures and topological reorganization of morphometric similarity networks in temporal lobe epilepsy with unilateral hippocampal sclerosis.
Zhu F, Tao B, He S … +9 more , Li Y, Gao Z, Liang Y, Pan C, Wu M, Zhou D, Lu P, Tang Y, Lui S
Epilepsia · 2026 Apr · PMID 41925386 · Publisher ↗
OBJECTIVE: To delineate morphometric similarity network (MSN) topological abnormalities and their underlying spatial transcriptomics in the normal-appearing cortex of unilateral mesial temporal lobe epilepsy with hippoca...
OBJECTIVE: To delineate morphometric similarity network (MSN) topological abnormalities and their underlying spatial transcriptomics in the normal-appearing cortex of unilateral mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS). METHODS: High-resolution T1-weighted magnetic resonance imaging (MRI) from 109 unilateral mTLE-HS patients (64 left, 45 right) and 90 matched controls were analyzed to construct individual-level MSNs by integrating five cortical morphometric features. Graph-theoretical analysis quantified global and local network topology, and machine-learning models assessed their values in patient identification and epileptogenic lateralization, with performance further evaluated in an independent validation dataset. Further connectome-transcriptome association analyses linked these macroscale topological abnormalities to the microscale substrates in specific gene expressions, biological pathways, cellular compositions, and neurodevelopmental windows. RESULTS: Patients exhibited global small-worldness increase and local nodal reorganizations, with hyper-connectivity in default mode and limbic networks and hypo-connectivity in temporo-occipital cortex. These MSN-topology abnormalities enabled accurate patient classification (77.4%) and epileptogenic lateralization (83.2%), driven predominantly by features from limbic network (40.0% and 41.1%, respectively). These performances were reproducible in an independent validation dataset (classification accuracy = 75.4%, lateralization accuracy = 77.1%). Spatial transcriptomics mapped the MSN-topology alterations to expression of genes enriched in RNA processing and mitochondrial energy metabolism, including key epilepsy risk genes such as DNM1 and PPFIA3. These genes showed enriched expression in excitatory neurons, astrocytes, and oligodendrocytes, peaking during neurodevelopment in early-fetal striatum and neonatal-to-childhood cortex. SIGNIFICANCE: MSN topology delineates the pattern of cortical network reorganization in mTLE-HS, aiding in patient identification and lateralization. The convergence of these macroscale connectomic alterations with microscale transcriptomic profiles points to an RNA-metabolic interplay that shapes cortical vulnerability of mTLE-HS in a progressive way.
Neonatal developmental and epileptic encephalopathy with movement disorder and arthrogryposis: A shared phenotype across brain-expressed sodium channelopathies.
Gverdtsiteli S, Ortiz S, Brünger T … +41 more , Furia F, Barba C, Bjørg-Hammer T, Borggraefe I, Caraballo R, Cirak S, Espeche A, Fazeli W, Guerrini R, Juanes M, Kassahn K, Kinali M, Krämer J, Kröll J, Herrero MCM, Oegema R, Ounap K, Peñuela O, Platzer K, Prasad AN, Pujol A, Reinson K, Represa A, Roza E, Valenzuela GR, Rodríguez-Palmero A, Sallevelt S, Sanchez-Albiusa MI, Scheffer IE, Smid C, Stafstrom CE, Stattin EL, Suarez JR, Syrbe S, Valente KD, Wagner M, Wortmann S, Gardella E, Lal D, Brunklaus A, Møller RS
Epilepsia · 2026 Apr · PMID 41925334 · Publisher ↗
OBJECTIVE: Neonatal developmental and epileptic encephalopathy with movement disorder and arthrogryposis (NDEEMA) represents the most severe end of the gain-of-function (GOF) SCN1A disorder spectrum. Sporadic cases of co...
OBJECTIVE: Neonatal developmental and epileptic encephalopathy with movement disorder and arthrogryposis (NDEEMA) represents the most severe end of the gain-of-function (GOF) SCN1A disorder spectrum. Sporadic cases of congenital arthrogryposis have also been reported in individuals with SCN2A-, SCN3A-, and SCN8A-related developmental and epileptic encephalopathy. Here, we investigated whether NDEEMA occurs in other brain-expressed sodium channelopathies and characterized its features. METHODS: Individuals with the clinical phenotype of NDEEMA were identified through internal databases, an international network of epileptologists and geneticists, and the literature. Their clinical and genetic information was analyzed. A literature survey was conducted to review studies describing the functional effects of the pathogenic variants. RESULTS: Of 46 NDEEMA individuals, 25 harbored variants in SCN1A, 13 in SCN2A, one in SCN3A, and seven in SCN8A. Thirty-five different pathogenic/likely pathogenic missense variants were identified, all of which clustered in evolutionary conserved paralogous Na positions. Five individuals died in utero. Thirty-nine of 41 (95%) liveborn individuals developed neonatal epilepsy with tonic seizures and/or apnea. Thirty-one individuals tried sodium channel blockers, of whom 21 (68%) experienced seizure reduction. All individuals for whom information was available developed movement disorders, with myoclonus, dystonia, and tremor being the most common features. Literature review of functional studies revealed that nine NDEEMA variants, and the corresponding paralogues of 16 additional NDEEMA variants, have been biophysically characterized as GOF. SIGNIFICANCE: This study expands the phenotype of NDEEMA from SCN1A to its paralogue sodium channel genes expressed in the brain: SCN2A, SCN3A, and SCN8A.
Systematic statistical analysis of change in SEIzure interVAL with diazepam nasal spray supports this novel clinical endpoint for immediate-use seizure medication.
Kerr WT, McFarlane KN, Ngo LY … +2 more , Carrazana E, Rabinowicz AL
Epilepsia · 2026 Apr · PMID 41919765 · Publisher ↗
OBJECTIVE: Appropriate endpoints for daily antiseizure medications may differ from those for intermittent, immediate-use seizure medications (ISMs). The observed interval between seizure clusters over time (SEIzure inter...
OBJECTIVE: Appropriate endpoints for daily antiseizure medications may differ from those for intermittent, immediate-use seizure medications (ISMs). The observed interval between seizure clusters over time (SEIzure interVAL [SEIVAL]) has been proposed as a novel effectiveness endpoint for ISMs. SEIVAL was initially identified pragmatically. This post hoc analysis evaluated how the study timeline and participant characteristics could impact the measurement of SEIVAL using data from an open-label study of intermittent treatment with diazepam nasal spray. METHODS: This analysis includes data from a long-term, phase 3 safety study of diazepam nasal spray, which enrolled patients aged 6-65 years with epilepsy and seizure clusters (NCT02721069). Study timeline and participant characteristic choices were evaluated systematically to determine the impact on effect size, and thereby statistical power, using data regarding individual treated seizure clusters. In this strategy, the date of the first treated seizure cluster constituted day 1 of the baseline period; consecutive 70-day periods were used for analysis. The change in SEIVAL for each patient was calculated using each measured SEIVAL for that patient in the primary outcome period (days 71-140) minus that patient's mean SEIVAL in the baseline period (days 1-70) with mixed effects linear regression. RESULTS: Mean SEIVAL increased from 13 days at baseline (days 1-70) to 24 days in the primary outcome period (days 71-140, p < .0001). SEIVAL lengthening was seen in adults, adolescents (ages 6-17 years), and children (ages 6-12 years), with further lengthening past 140 days in adolescents and children. SEIVAL lengthened more in participants with <1 SEIVAL per 2 weeks at baseline than higher SEIVAL frequency. SIGNIFICANCE: This systematically planned analysis expands on and reinforces the previous pragmatic analysis that introduced the SEIVAL metric. The present analysis provides a novel framework for future studies of intermittently administered ISMs to treat seizure clusters such as diazepam nasal spray.
Artificial intelligence-assisted detection of epileptic spasms using electroencephalographic-video analysis.
Wan L, Lin N, Wang W … +13 more , Liang Z, Dong Y, He H, Chen J, Fan Y, Liu T, Wang H, Cheng W, Lu G, Wang J, Zhang B, Lu Q, Yang G
Epilepsia · 2026 Jun · PMID 41914624 · Full text
OBJECTIVE: This study was undertaken to develop and validate an artificial intelligence (AI) diagnostic tool using hybrid electroencephalographic (EEG)-video signals for automatic epileptic spasms (ES) detection. METHODS...
OBJECTIVE: This study was undertaken to develop and validate an artificial intelligence (AI) diagnostic tool using hybrid electroencephalographic (EEG)-video signals for automatic epileptic spasms (ES) detection. METHODS: This retrospective cohort study with internal cross-validation and multicenter external validation was conducted from July 2022 to May 2025. It included 252 patients with ES from Chinese PLA General Hospital and 60 from three other medical centers. We developed a multimodal fusion approach combining video and electrophysiological signals. All EEG data were segmented into continuous 4-s pages. The internal cohort consisted of 212 patients (723.4 h video-EEG, 7348 ES, and 643 215 non-ES segments). Clinical validation involved 100 patients across four datasets (212.2 h, 5709 ES and 185 207 non-ES segments) plus 78 controls without ES (218.1 h, 196 249 segments, used for false alarm rate analysis). Primary outcomes included sensitivity, specificity, accuracy, precision, and F1 score versus electroencephalographer interpretation. RESULTS: In internal cross-validation, the hybrid EEG-video model achieved superior performance compared to current EEG-only models (area under the precision-recall curve = .7334, 95% confidence interval [CI] = .7118-.7539, area under the receiver operating characteristic curve = .9820, 95% CI = .9782-.9856). In the clinical validation dataset, the model demonstrated diagnostic sensitivity (.735, 95% CI = .673-.822) and specificity (.995, 95% CI = .992-.996) comparable to experienced electroencephalographers. With AI assistance, all electroencephalographers showed improved sensitivity trends, with one rater showing a marked improvement from .620 (95% CI = .532-.699) to .792 (95% CI = .757-.821). Notably, specificity did not decline significantly for any of the raters. In samples containing subtle ES, machine-assisted recognition significantly improved sensitivity by 16%-21% for all electroencephalographers (p < .01). The model maintained low false alarm rates (.16‰) across different patient populations including healthy controls and epilepsy patients without ES. SIGNIFICANCE: This AI diagnostic tool achieves clinical performance comparable to senior electroencephalographers when applied independently for ES detection, with greater robustness in detecting subtle ES. When used collaboratively with clinicians, it could enhance diagnostic sensitivity while maintaining high specificity. The technology addresses critical diagnostic challenges in pediatric epilepsy care and shows promise to reduce health care inequities in resource-limited settings lacking specialized expertise.
Mortality in functional seizures: Evidence from a large electronic health records dataset.
Kanaan RA, Berlot R, Pollak T … +2 more , Reuber M, Popkirov S
Epilepsia · 2026 Mar · PMID 41914236 · Publisher ↗
OBJECTIVE: Several studies have found that people with functional seizures (FS) have increased mortality, approaching that of epilepsy (epileptic seizures [ES]). The small numbers of deaths in these studies make it uncle...
OBJECTIVE: Several studies have found that people with functional seizures (FS) have increased mortality, approaching that of epilepsy (epileptic seizures [ES]). The small numbers of deaths in these studies make it unclear whether they can be attributed to comorbidities. We used a very large electronic health database to compare mortality in FS and ES, controlling for comorbidity. METHODS: We searched the TriNetX database for people with FS and no ES, people with ES and no FS, and people with neither FS nor ES (NS). We compared mortality while controlling for demographics and comorbid conditions. RESULTS: We identified 1 916 787 people with ES, 32 854 people with FS, and 21 053 667 healthy controls. FS had rates of mental and physical comorbidities that were higher than NS and, for most categories, higher than ES. The risk of death (hazard ratio [HR]) in ES compared to FS was 2.99 (95% confidence interval [CI] = 2.81-3.18), which was reduced to 2.07 (95% CI = 1.92-2.24) when matched for 31 demographic and health factors. The risk of death in NS compared to FS was .56 (95% CI = .53-.59); after matching for demographics and mood disorders, this was .48 (95% CI = .44-.53). Matched sensitivity analyses suggest this was particularly pronounced in the year following diagnosis (HR = .39, 95% CI = .33-.47) and in the 5th decade of life (HR = .38, 95% CI = .27-.52). SIGNIFICANCE: FS confers approximately doubled mortality over that conferred by its comorbidities, although still only half of that conferred by ES, most prominently after diagnosis and in early middle age.
Artificial intelligence for adaptive neuromodulation in drug-resistant epilepsy.
Daraie AH, Damiani A, Khoshkhou M … +8 more , Sanchez LA, Smith RJ, Agashe SH, Gonzalez-Martinez JA, Hopp J, Charles AS, Sarma SV, Kang JY
Epilepsia · 2026 Mar · PMID 41914206 · Publisher ↗
Drug-resistant epilepsy (DRE) affects nearly one third of people with epilepsy and is associated with substantial cognitive, psychiatric, and mortality burdens. For patients who are not candidates for resection or laser...
Drug-resistant epilepsy (DRE) affects nearly one third of people with epilepsy and is associated with substantial cognitive, psychiatric, and mortality burdens. For patients who are not candidates for resection or laser interstitial thermal therapy, neuromodulation therapies such as vagus nerve stimulation, deep brain stimulation, and responsive neurostimulation offer an important and established therapeutic option that can provide substantial, often life-changing benefits, although clinical response varies widely and typically requires prolonged, iterative optimization. Epilepsy is increasingly understood as a disorder of distributed and dynamic brain networks, in which seizure generation, propagation, and termination reflect interactions among connected regions that evolve over time. In this setting, improving neuromodulation requires precise and patient-specific decisions across the treatment workflow. This perspective reframes neuromodulation as a control problem organized around four interdependent clinical questions: who is most likely to benefit, where to deliver stimulation within an individual's epileptic network, when to apply stimulation relative to evolving seizure risk, and how to configure and adapt stimulation parameters over time. Artificial intelligence (AI) may provide a unifying framework for addressing these questions in a personalized and data-driven manner. AI-guided response prediction could estimate the likelihood of benefit before implantation. AI-driven network analyses could identify optimal stimulation targets based on circuit influence rather than seizure onset alone. AI-based state estimation could enable continuous forecasting of seizure risk across short-term, circadian, and multidien timescales, supporting stimulation during periods of rising vulnerability rather than solely in response to detected seizures. Also, AI-enabled adaptive control could optimize stimulation parameters through state-dependent strategies that balance efficacy, safety, tolerability, and energy constraints as brain dynamics evolve. This review synthesizes biological, clinical, and computational advances to outline a roadmap for safe, interpretable, and individualized AI-guided neuromodulation in DRE.
Functional connectivity in self-limited epilepsy with centrotemporal spikes increases with epilepsy duration and interictal spike exposure.
Vasitas ME, Menchaca MS, Goad BS … +4 more , She X, Lee-Messer C, He Z, Baumer FM
Epilepsia · 2026 Mar · PMID 41910930 · Publisher ↗
OBJECTIVE: To determine whether persistent exposure to interictal spikes is associated with progressive changes in functional connectivity in children with self-limited epilepsy with centrotemporal spikes (SeLECTS). METH...
OBJECTIVE: To determine whether persistent exposure to interictal spikes is associated with progressive changes in functional connectivity in children with self-limited epilepsy with centrotemporal spikes (SeLECTS). METHODS: Connectivity was calculated from electroencephalograms (EEGs) of 68 children with SeLECTS and 65 age- and sex-matched controls using the weighted phase lag index. First, we assessed whether connectivity increased with longer epilepsy duration, categorizing duration based on time since first seizure (less vs. greater than 6 months). Second, in a subset of 19 SeLECTS children with repeated EEGs, we assessed whether trajectory of connectivity over time differed based on persistence versus resolution of spikes. Connectivity during sleep and wakefulness was examined separately. RESULTS: During sleep, connectivity was lowest in controls, intermediate in patients with recent onset epilepsy, and highest in those with longer epilepsy duration. Elevations in connectivity were greatest within the right occipital region at onset and became more widespread with longer epilepsy duration, especially increasing in the left temporal region. During wakefulness, connectivity in recent onset epilepsy trended lower than controls, whereas longer duration epilepsy trended higher, such that the two epilepsy groups differed significantly from each other but not from controls. In the cohort of children with repeated EEGs, patients with persistent spikes showed increasing connectivity over time in sleep, whereas those with spike resolution demonstrated decreasing connectivity over time. There were no significant changes in awake connectivity over time regardless of spike persistence or resolution. SIGNIFICANCE: Functional connectivity in SeLECTS increases progressively with longer duration of spike exposure, suggesting that ongoing spikes drive neural network alterations. Spikes are a potential treatment target to prevent progressive brain network disruption and preserve cognitive outcomes.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe