Epilepsia[JOURNAL]
Sun
200 papers
SUDEP and mortality in developmental and epileptic encephalopathies: A meta-analysis of randomized clinical trials and extension studies.
Moro P, Borioni MS, Mazzeo A … +3 more , Cocchi E, Bonaventura CD, Cerulli Irelli E
Epilepsia · 2026 Jun · PMID 42360057 · Publisher ↗
OBJECTIVE: Developmental and epileptic encephalopathies (DEEs) are associated with high premature mortality and increased risk of sudden unexpected death in epilepsy (SUDEP). However, epidemiological data remain limited,...
OBJECTIVE: Developmental and epileptic encephalopathies (DEEs) are associated with high premature mortality and increased risk of sudden unexpected death in epilepsy (SUDEP). However, epidemiological data remain limited, particularly for specific syndromes such as Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and infantile epileptic spasms syndrome (IESS). To address this gap, we conducted a Bayesian meta-analysis of randomized controlled trials (RCTs) and corresponding long-term open-label extension (OLE) studies. METHODS: All-cause mortality and SUDEP incidence rates were estimated using hierarchical Bayesian models with moderately informative priors derived from the literature. A negative binomial likelihood was used for all-cause mortality, whereas a Poisson likelihood was used for SUDEP. Subgroup analysis were conducted for DS, LGS, and IESS. RESULTS: Thirty-seven RCTs and 15 OLE studies were included, comprising 3757 patients with DEEs (2221 LGS, 998 DS, 369 IESS, and 169 other DEEs). Across pooled data, 37 deaths occurred, including 2 definite, 12 probable, and 1 possible SUDEP. In the overall DEE population, the Bayesian posterior median estimated mortality rate was 8.76 per 1000 person-years (PY; 95% credible interval [CrI], 5.50-13.89), and SUDEP rate was 4.32 per 1000 PY (95% CrI, 2.66-6.64). In LGS, mortality was 7.05 per 1000 PY and SUDEP was 3.4 per 1000 PY. In DS, mortality was 8.0 per 1000 PY, with a SUDEP rate of 7.59 per 1000 PY. In IESS, mortality was 9.41 per 1000 PY and SUDEP was 2.79 per 1000 PY. SIGNIFICANCE: SUDEP accounted for approximately half of deaths in the overall DEE population and in LGS, with a proportionally greater contribution in DS. Potential trial-related underestimation should be considered when interpreting these findings, as features of trial-based datasets could have contributed to lower observed mortality and SUDEP estimates. Prospective population-based studies are needed to more accurately define the real-world incidence of SUDEP in DEEs.
Acute and Long-Term EEG and seizure characteristics in new onset refractory status epilepticus (NORSE).
Gilani K, Hanin A, Gaspard N … +31 more , Batra A, Behrndt L, Day GS, Demeret S, Eschbach K, Foreman B, Gerard EE, Gofton TE, Gopaul MT, Haider HA, Hantus ST, Cobos-Hernandez C, Jimenez AD, Jongeling A, Kandula P, Kang P, Kazazian K, Kellogg M, Kim M, Farias-Moeller R, Morales M, Navarro V, Pimentel CM, Ramirez A, Steriade C, Struck AF, Taraschenko O, Wainwright MS, Zhou DJ, Hirsch LJ, Yoo JY
Epilepsia · 2026 Jun · PMID 42359767 · Publisher ↗
OBJECTIVE: This study was undertaken to examine acute and chronic electroencephalographic (EEG) and seizure characteristics in new onset refractory status epilepticus (NORSE). METHODS: Multicenter inpatient and follow-up...
OBJECTIVE: This study was undertaken to examine acute and chronic electroencephalographic (EEG) and seizure characteristics in new onset refractory status epilepticus (NORSE). METHODS: Multicenter inpatient and follow-up clinical and EEG data were analyzed using International League Against Epilepsy definitions and American Clinical Neurophysiology Society (ACNS) EEG terminology. RESULTS: Forty-four patients were included from the Yale NORSE/FIRES Biorepository (median age = 29 years, 33 female, 38 cryptogenic). Nine hundred twenty inpatient EEG days were reviewed (median = 13.5 days/patient). Presenting status epilepticus (SE) types included 24 convulsive SE (CSE), five focal-motor (FMSE), and 15 nonconvulsive (NCSE). Of 39 patients with post discharge follow-up (median = 14.7 months), 61.5% (n = 24) had seizures and required more antiseizure medications than seizure-free patients (median = 4 vs. 1, p < .001). Inpatient EEG captured epileptiform discharges in all and periodic discharges in 38 patients. Seizures were captured in 38 patients: 33 electrographic (11 only electrographic) and 27 electroclinical. Total seizure burden ranged 6.5-29 615.0 min (median = 50.7). Seizures fulfilling ACNS EEG criteria for SE were captured in 20 patients; two had CSE and the remainder NCSE with coma, nine of whom also had FMSE. Inpatient seizure days (median = 50.0 vs. 15.5%, p = .004) and seizure burden (median = 42.9 vs. 0 min, p = .009) were higher in the first half of monitored days. Interictal findings were equally present and did not predict postdischarge seizures, whereas electroclinical seizures (90.9% vs. 45.5%, p = .037), seizure burden (median = 116.8 vs. 32.5 min, p = .045), and proportion of seizure days (36.3% vs. 20.0%, p = .037) did. Among 12 patients with follow-up EEGs (median = 19.6 months post onset), posterior-dominant rhythm (PDR) returned in nine; five had periodic discharges, and three had seizure captured. SIGNIFICANCE: Seizures are most commonly convulsive upon presentation and nonconvulsive or clinically subtle throughout the inpatient course in NORSE. Inpatient seizures, but not interictal abnormalities, occur earlier in the inpatient course and presence of electroclinical seizures, seizure burden, and proportion of seizure days but not interictal findings are associated with postdischarge seizures. Although return of PDR reflects neurological recovery, seizure persistence and EEG abnormalities post-NORSE are common.
Accuracy of the rapid-response electroencephalography's Automated Seizure Burden Estimator: A follow-up validation study of version 8 (AccuRASE II).
Sheikh ZB, Fong MWK, Dhakar MB … +12 more , Fang W, Ayub N, Molino J, Haider HA, Foreman B, Gilmore EJ, Mizrahi M, Karakis I, Schmitt S, Osman G, Yoo JY, Hirsch LJ
Epilepsia · 2026 Jun · PMID 42347801 · Publisher ↗
OBJECTIVE: Ceribell Inc.'s point-of-care electroencephalographic (EEG) system and artificial intelligence-based Automated Seizure Burden Estimator (ASBE; ClarityPro) have US Food and Drug Administration clearance for dia...
OBJECTIVE: Ceribell Inc.'s point-of-care electroencephalographic (EEG) system and artificial intelligence-based Automated Seizure Burden Estimator (ASBE; ClarityPro) have US Food and Drug Administration clearance for diagnosing electrographic status epilepticus (ESE). The AccuRASE study using ASBE version 6 (V6) showed high negative predictive value (NPV) but limited sensitivity and positive predictive value (PPV) at certain thresholds. Version 8 (V8) is the updated algorithm trained with additional EEG samples. METHODS: We tested V8 on the previously used rapid-response EEG test dataset (not used to train V8). Sensitivity, specificity, PPV, and NPV were compared against blinded expert annotations. ESE, ESE and possible ESE (ESE/pESE), electrographic seizures (ESz), and Esz with highly epileptiform patterns (Esz/HEPs) at burden thresholds of >1%, >10%, >20%, >50%, and >90% were analyzed. Additionally, we evaluated the built-in ESE and ESE/pESE alerts (≥90% over 5 min, ≥20% over 1 h, or ≥10 continuous minutes of seizure). RESULTS: V8 showed 100% sensitivity at lower thresholds (>10%-20%) for ESE (V6 .86), without a specificity loss (V8 .9 vs. V6 .85), and retained NPV (V8 1.0 vs. V6 .99). Sensitivity at 50% threshold was .86 for ESE (V6 .71), and specificity was .94 (V6 .91); PPV for ESE was 30% for ESE and 80% for ESE/pESE. The specificity for ESE remained high for 90% burden (V8 .96, V6 .97) but the sensitivity dropped (.29 vs. V6 .43). Sensitivity was lower for ESz/HEPs (.54 → .44 at >10% threshold), although the algorithm is not designed to detect HEPs. Built-in alert analysis showed significantly improved sensitivity for ESE (.57 → .86); specificity and NPV remained high (>.94). SIGNIFICANCE: ASBE V8 showed meaningful improvements in sensitivity, continued excellent NPV, and improved built-in alert accuracy for ESE and ESE/pESE. The best seizure burden threshold for ruling out ESE now is 20% (vs. 10% with V6) and that for ruling in ESE/pESE with reasonable certainty is 50% (vs. 90% with V6).
Variability in epilepsy polygenic risk prediction across Taiwanese population and clinical cohorts.
Ke YS, Tsai MH, Ho CR … +36 more , Chou CY, Chen HH, Stevelink R, Chen S, Chen PC, Liu YT, Tung H, Hsiao TH, Tseng SH, Chan L, Lee TH, Cheng CK, Jeng JS, Lin CH, Hsu CY, Yang YH, Yang SF, Fan YC, Yang FC, Sung YF, Lin SZ, Wang TF, Liu YH, Chu YC, Chen M, Chang MY, Lee SL, Chang CC, Huang YC, Cheng WM, Chen SS, Su YH, Sung SF, Lee MC, Chen JT, Feng YA
Epilepsia · 2026 Jun · PMID 42347787 · Publisher ↗
OBJECTIVE: This study was undertaken to evaluate the predictive, stratification, and prognostic utility of polygenic risk scores (PRSs) for epilepsy in three Taiwanese cohorts comprising more than 7000 cases among more t...
OBJECTIVE: This study was undertaken to evaluate the predictive, stratification, and prognostic utility of polygenic risk scores (PRSs) for epilepsy in three Taiwanese cohorts comprising more than 7000 cases among more than 600 000 individuals, thereby addressing the limited evidence on PRS performance in non-European populations. METHODS: Leveraging results from the latest multiancestry genome-wide association study (GWAS), we calculated PRS for all epilepsy, genetic generalized epilepsy (GGE), and focal epilepsy (FE) in two population cohorts-Taiwan Biobank-National Health Insurance Research Database (TWB-NHIRD; N ~ 105 K) and Taiwan Precision Medicine Initiative (TPMI; N ~ 500 K), with cases defined by International Classification of Diseases codes and medications-and a clinically ascertained sample (Taiwanese subset of the Epi25 consortium [Epi25-TWN]; N = 1140). PRS performance was assessed through lifetime risk models, age-at-onset stratifications, and phenome-wide association studies (PheWASs). RESULTS: PRS performance varied substantially by cohort, epilepsy type, and age at onset. GGE PRS had the strongest effect on GGE in Epi25-TWN (per-unit odds ratio [OR] = 1.65 [95% confidence interval (CI) = 1.24-2.23], p = 8.3 × 10, R = 3.2%) but a weaker effect in TWB-NHIRD and TPMI (ORs = 1.09-1.13 [95% CI = .98-1.23], p = .002-.057, R = .14%-.22%). FE PRS effects on FE were more consistent but modest (ORs = 1.02-1.16 [95% CI = .97-1.33]). No prognostic value of PRS was found in predicting epilepsy from syncope or unspecified seizures. Individuals in the top 5% GGE PRS had >4-fold increased risk in Epi25-TWN but <1.5-fold in the others. Restricting to earlier onset cases strengthened PRS signals in population cohorts, particularly for GGE, with PheWAS analysis revealing epilepsy-specific associations. PRS effects were generally comparable but attenuated relative to European studies. SIGNIFICANCE: Cohort design and phenotyping accuracy strongly influence the assessment of the predictive value of epilepsy PRS, highlighting caution in clinical interpretation. Incorporating richer phenotypic data and more diverse GWASs will be crucial to enhancing its applicability and clinical potential.
Beyond congenital anomalies, the impact of sodium valproate exposure in utero on long-term health and well-being: A contribution from the ConcePTION project.
Wells PA, Richardson JL, Astill D … +11 more , Bluett-Duncan M, Bromley RL, Clayton-Smith J, Cole S, Cozens J, Keely K, Morris J, Murphy E, Turnpenny PD, Williams J, Yates LM
Epilepsia · 2026 Jun · PMID 42347559 · Publisher ↗
OBJECTIVE: Sodium valproate (VPA) is an established teratogen that is prescribed worldwide. Although congenital anomalies and neurodevelopmental impairments are well described in those affected by in utero VPA exposure,...
OBJECTIVE: Sodium valproate (VPA) is an established teratogen that is prescribed worldwide. Although congenital anomalies and neurodevelopmental impairments are well described in those affected by in utero VPA exposure, limited data are available regarding the physical health impacts. We aimed to document, via caregiver reporting, the physical health outcomes for a cohort of in utero VPA-exposed individuals compared with an unexposed group. METHODS: This cross-sectional observational study collected primary data via questionnaire from primary caregivers of individuals exposed and unexposed to VPA in utero. Information collected related to maternal health, pregnancy, offspring health and neurodevelopment. Participants were recruited from the UK, Ireland, New Zealand, the United States, and Australia. Reported physical health was compared between those exposed to VPA monotherapy in utero (n = 88) and an unexposed group (n = 18). RESULTS: Physical health concerns were reported in a median of 6 of 12 organ systems for those with VPA exposure of 1000 mg per day or greater, 5 systems with exposure less than 1000 mg VPA per day, and 1 in the unexposed group. The VPA-exposed group reported poorer health (p < .001), increased difficulty (p < .001), pain or distress (p < .001), and increased limitation of daily activities (p < .001). Reported health complaints were wide ranging and extended beyond congenital anomalies. SIGNIFICANCE: This study highlights increased reporting of physical health challenges in those exposed to VPA in utero, the multimorbidity impact of which affects quality of life and can persist into adulthood. Further study is warranted to ascertain accurate prevalence of these symptoms among individuals harmed by VPA in utero.
Gamma suppression correlates with thalamic stimulation therapeutic response in intractable epilepsy.
Sanger ZT, Zhang X, Lisko T … +8 more , Farooqi H, Ventz S, Pati S, Henry TR, Darrow DP, Park MC, Netoff TI, McGovern RA
Epilepsia · 2026 Jun · PMID 42334259 · Publisher ↗
OBJECTIVE: In patients with drug-resistant epilepsy who undergo anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS), efficacy is assessed months after therapy initiation and clinicians have no guidance wh...
OBJECTIVE: In patients with drug-resistant epilepsy who undergo anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS), efficacy is assessed months after therapy initiation and clinicians have no guidance when choosing stimulation parameters due to the lack of real-time biomarkers. Here, we identified acute and chronic suppression of slow gamma local field potential (LFP) oscillations (SGOs) (20-50 Hz) in the ANT as a novel electrophysiological biomarker correlated with therapeutic response. METHODS: Participants enrolled in an ongoing prospective ANT-DBS parameter optimization trial (N = 11) were analyzed retrospectively for the effects of stimulation on ANT LFPs. One-minute baseline and stimulation ANT LFPs were captured across follow-up visits using a Medtronic Percept, testing different stimulation settings around the Stimulation of the Anterior Nucleus of the Thalamus in Epilepsy (SANTE) trial clinical setting (145 Hz, 90 μs) in the clinic. Aperiodic component detrended ANT LFP power spectral density responses during stimulation were compared against each baseline responses. Participants kept a seizure diary, where responders were those who achieved greater than a 50% seizure frequency reduction compared to their pre-DBS seizure frequency. RESULTS: In the seven participants exhibiting SGOs, six were responders. Progressive suppression ("gamma fade") of SGOs under chronic stimulation correlated with long-term seizure reduction in five of six responders. Acute stimulation in-clinic with multiple settings suppressed SGOs in four of five responders, challenging fixed-programming paradigms, with only one responder using the clinical gold standard parameters at the last follow-up visit. SIGNIFICANCE: These findings establish SGO suppression as a potential multiscale biomarker for responder identification, parameter titration, and therapeutic tracking for precise, biomarker-guided intervention.
Effectiveness and tolerability of fenfluramine in pediatric and adult patients with developmental and epileptic encephalopathies: A multicenter, retrospective, real-world clinical-practice study.
Villanueva V, González-Alguacil E, Smeyers P … +27 more , Hernández S, Soto-Insuga V, Fernández-Cabrera A, Olivié L, de Santos T, Parejo B, Iacampo L, Ortuño B, Aparicio J, Fuentes M, Rodriguez-Uranga J, Martínez-Agredano P, Estévez JC, Aledo-Serrano A, Martin-Alvarez R, Conejo D, Baena B, Mercedes-Álvarez B, López Y, Sierra-Marcos A, Trincado-Lamuño R, Ennazeh M, de la Aleja JG, Renau J, Castro-Vilanova MD, Romero-Aguilera F, Serratosa JM
Epilepsia · 2026 Jun · PMID 42334048 · Publisher ↗
OBJECTIVE: Developmental and epileptic encephalopathies (DEEs) are characterized by drug-resistant seizures and developmental slowing/regression. We examined the efficacy and tolerability of fenfluramine (FFA) in pediatr...
OBJECTIVE: Developmental and epileptic encephalopathies (DEEs) are characterized by drug-resistant seizures and developmental slowing/regression. We examined the efficacy and tolerability of fenfluramine (FFA) in pediatric and adult patients with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and other DEEs. METHODS: In this multicenter, retrospective, real-world study, FFA treatment was initiated ≥12 months before database closure. Data from patients' charts at 3, 6 and 12 months were recorded in the Spanish Epilepsy Society's DEEs registry. Effectiveness endpoints included seizure reductions of 100%, ≥75%, and ≥50% (responder), median percent seizure reduction, and seizure worsening. Safety endpoints included adverse event (AE) rates. RESULTS: The study included 166 patients (LGS, n = 84; DS, n = 42; other DEE, n = 40; mean age 16.6 ± 12.1 years [111 pediatric, median 10.1 years; 55 adult, median 26.5 years]). Patients had a median of 3 prior failed anti-seizure medications (ASMs). At 12 months, the median FFA dose was 0.49 mg/kg/day, with 77.1% treatment retention. There was a 68.8% median reduction in seizure frequency between baseline and 12 months (p < .001), with significant reductions across all diagnostic groups (LGS, p < .001; DS, p < .001; other DEE, p = .004). The 12-month ≥50% responder rate was 61%, with no statistically significant differences according to age. At 12 months, there were significant reductions in the mean number of concomitant ASMs (p = .004) and the proportion of patients requiring rescue medication (p < .001). Meaningful improvements in Clinical Global Impression scores for cognition (59.3% of patients), behavior (40.9%), sleep (24.3%), and caregiver (44.8%) domains were observed. At 12 months, AEs were reported in 68.1% of patients (mostly mild-to-moderate) and AEs leading to discontinuation in 12%, with no significant differences according to age. SIGNIFICANCE: FFA was effective, with predictable tolerability, in patients with different DEEs and seizure types, supporting its use as an effective treatment option in pediatric and adult patients with DEEs.
Insights into ANKRD11-related epilepsy from 163 people.
Su S, Ma J, Zhang Q … +4 more , Hu W, Ren Y, Zhang W, Zhang H
Epilepsia · 2026 Jun · PMID 42322264 · Publisher ↗
OBJECTIVE: Ankyrin repeat domain 11 gene (ANKRD11) is the key disease gene for autosomal dominant KBG syndrome, and a subset of affected individuals develop epilepsy. However, comprehensive characterization of epilepsy-r...
OBJECTIVE: Ankyrin repeat domain 11 gene (ANKRD11) is the key disease gene for autosomal dominant KBG syndrome, and a subset of affected individuals develop epilepsy. However, comprehensive characterization of epilepsy-related phenotypes and genotype-phenotype correlations in ANKRD11 variant carriers remains limited. We aimed to integrate a single-center cohort with previously reported cases to delineate the epilepsy phenotype spectrum, evaluate genotype-phenotype associations, and provide clinical information for ANKRD11-related epilepsy. METHODS: Whole exome sequencing was performed in nine unrelated individuals identified at our center. In addition, a systematic search of PubMed (keywords: "ANKRD11" AND "epilepsy") was performed up to October 2025, and eligible cases were aggregated for pooled analyses of clinical features. RESULTS: We identified nine individuals with heterozygous ANKRD11 variants at our center; four had epilepsy, and three variants were novel. In silico analyses suggested stronger predicted deleterious effects for missense variants within repression domain (RD; including RD1 and RD2)-related regions, and localization to RD2 may be associated with potential genotype-phenotype correlations. In a pooled cohort of 163 individuals with ANKRD11 variants and epilepsy, seizure onset occurred at a median age of 4.0 years (interquartile range = 1.5-8.0). Focal and generalized epilepsies were similarly represented, and absence seizures were reported in 22.8%. Brain magnetic resonance imaging (MRI) abnormalities were observed in 45.9% of individuals with available data; 63.2% of patients in the overall cohort achieved seizure freedom, with 36.8% exhibiting drug-resistant epilepsy. Frameshift variants predominated (60.1%), and variants showed domain-specific enrichment, with missense variants clustering in RD2 and truncating variants enriched outside RD2. Individuals with missense variants tended to have later onset, normal MRI, and higher seizure control rates. SIGNIFICANCE: This integrated analysis expands the mutational spectrum of ANKRD11 and provides a consolidated genotype-phenotype landscape of ANKRD11-related epilepsy. Variant class and domain-specific clustering patterns, together with differences in clinical profiles and outcomes, support domain-informed variant interpretation and may improve clinical counseling and management for patients.
Paroxysmal slow waves mark ictal networks.
Boyer-Aymé FJM, Imtiaz H, Prager O … +11 more , Swissa E, Ahmad AA, Serlin Y, Aboghazleh R, Goldberg I, Caller MBN, Tamir I, Shor O, Whatley B, Benninger F, Friedman A
Epilepsia · 2026 Jun · PMID 42322257 · Publisher ↗
OBJECTIVE: Epilepsy diagnosis and treatment monitoring are hindered by the episodic, heterogeneous expression of seizures and by normal-appearing scalp electroencephalography (EEG) in many patients. We previously describ...
OBJECTIVE: Epilepsy diagnosis and treatment monitoring are hindered by the episodic, heterogeneous expression of seizures and by normal-appearing scalp electroencephalography (EEG) in many patients. We previously described paroxysmal slow-wave events (PSWEs), brief epochs of broadband slowing detectable on EEG in people with epilepsy. In the present study, we sought to further define the clinical significance of this biomarker. METHODS: We used intracerebral and epidural recordings in a paraoxon rat model of temporal lobe epilepsy, as well as long-term video-EEG monitoring (LTM) in patients with temporal lobe epilepsy undergoing intracerebral recordings combined with scalp EEG, or with scalp EEG alone. RESULTS: We show that PSWEs arise preferentially in temporo-frontal networks, co-occur with global slowing, and increase during both spontaneous and pharmacologically induced seizures. Epidurally recorded PSWEs were temporally coupled to deep temporal discharges and were bidirectionally modulated by γ-aminobutyric acid (GABA)ergic agents (increased with pentylenetetrazol and decreased with pentobarbital). In patients with temporal lobe epilepsy, simultaneous intracerebral recordings and scalp EEG showed that scalp PSWEs mirrored hippocampal spike-and-wave activity. PSWEs were more frequent during the preictal and ictal periods than during the interictal baseline, a finding confirmed in a retrospective analysis of 137 seizures from 18 patients recorded with scalp EEG alone. SIGNIFICANCE: These data indicate that surface PSWEs can index remote epileptiform activity and support their use as a quantitative, noninvasive biomarker for detecting EEG-silent deep foci and for pharmacodynamic evaluation.
Tonic-clonic seizures captured during ambulatory video-EEG are frequently unreported.
Nurse ES, French J, Wong V … +1 more , Cook M
Epilepsia · 2026 Jun · PMID 42322243 · Publisher ↗
OBJECTIVE: Tonic-clonic seizures (TCSs) are widely regarded as clinically obvious, yet seizure counts used for treatment decisions and risk counseling often rely on patient or caregiver diaries. We sought to quantify the...
OBJECTIVE: Tonic-clonic seizures (TCSs) are widely regarded as clinically obvious, yet seizure counts used for treatment decisions and risk counseling often rely on patient or caregiver diaries. We sought to quantify the frequency of unreported TCSs during prolonged ambulatory video-EEG (vEEG) monitoring and examined associations with electrographic-onset subtype and patient characteristics. METHODS: We conducted a retrospective cohort study of routinely collected ambulatory vEEG from a single national Australian service (January 2018-June 2024). Studies were eligible if the patient had epilepsy and at least one objectively captured TCSs. Reporting status was derived from diary entries and post-study questioning, and classified as reported vs unreported. The primary descriptive outcome was patient-level reporting status across captured TCSs: all captured TCSs reported, some captured TCSs reported, or no captured TCSs reported. Event-level reporting status was used for seizure-level descriptive summaries and patient-clustered analyses. Event-level associations were examined using patient-clustered generalized estimating equations, and patient-level subgroup comparisons used nonparametric and categorical tests. RESULTS: Among 130 patients with objectively captured TCSs, 69 of 130 (53.1%) reported all captured TCSs, 41 of 130 (31.5%) reported some but not all captured TCSs, and 20 of 130 (15.4%) reported no TCSs during monitoring. Overall, 61 of 130 patients (46.9%) had at least one unreported TCS. At the event level, 340 of 754 captured TCSs (45.1%) were unreported and identified only on review. Nineteen of 130 patients (14.6%; 95% confidence interval [CI] 9.0-21.9) had no documented prior TCS history in available service records and reported no TCSs during monitoring. Unreported event proportions were similar across focal-onset and generalized-onset TCSs, whereas sleep was associated with higher odds of underreporting. SIGNIFICANCE: In this selected ambulatory vEEG cohort, nearly half of patients with captured TCSs had at least one unreported TCS, including 15.4% who reported none during monitoring. These findings indicate that diary-based histories may underestimate convulsive seizure burden in some monitored patients, with implications for safety decisions, therapeutic escalation, and sudden unexpected death in epilepsy (SUDEP) counseling.
Stage 1 Plus: A phenotype-based framework for rational polytherapy in status epilepticus.
Magro G
Epilepsia · 2026 Jun · PMID 42313378 · Publisher ↗
Current guidelines for status epilepticus (SE) prioritize treatment with a benzodiazepine (BDZ), followed, if seizures continue, by sequential stepwise therapy. Yet this pragmatic framework does not fully capture the bio...
Current guidelines for status epilepticus (SE) prioritize treatment with a benzodiazepine (BDZ), followed, if seizures continue, by sequential stepwise therapy. Yet this pragmatic framework does not fully capture the biological heterogeneity apparent at first clinical evaluation. Some patients are treatment-naive but may already be at increased risk of early BDZ failure, because duration, semiology, etiology, or delayed recognition have moved the disorder into a less responsive state, in the context of time-dependent receptor trafficking and evolving pharmacoresistance. These presentations can be classified as Stage 1 Plus: a semiology- and etiology-based framework for a likely BDZ-resistant, high-risk phase of SE in which early polytherapy may be warranted. It includes prolonged SE (defined by semiology-adapted thresholds), nonconvulsive SE with coma, and acute symptomatic SE due to primary central nervous system disorders. Stage 1 Plus is proposed as a framework for prospective testing of biologically grounded polytherapy in selected SE phenotypes.
Mindfulness meditation increases interictal epileptiform discharges in meditation-naïve surgical epilepsy patients.
Soni S, Brochu K, Federico P … +3 more , Hader W, Kam JWY, Girgis F
Epilepsia · 2026 Jun · PMID 42299691 · Publisher ↗
OBJECTIVE: Meditation has widely recognized psychological and neuromodulatory benefits, yet its effects on epileptiform activity remain unclear. This study examined whether novice meditation modulates interictal epilepti...
OBJECTIVE: Meditation has widely recognized psychological and neuromodulatory benefits, yet its effects on epileptiform activity remain unclear. This study examined whether novice meditation modulates interictal epileptiform discharges (IEDs) in patients with drug-resistant epilepsy using intracranial electroencephalography (iEEG). METHODS: Twenty-seven meditation-naïve patients undergoing iEEG monitoring performed two meditation conditions, focused attention meditation (FAM) and open monitoring meditation (OMM), as well as two control conditions, story listening (STL) and classical music listening (CMM). IEDs were visually identified across the brain and manually labeled by an experienced neurologist. Linear mixed-effects models were applied to assess the effect of meditation on IED density (IEDs/min). Subjective meditative depth was evaluated using the Meditation Depth Questionnaire (MEDEQ), and associations between IED density and subjective experiences were examined. RESULTS: Both focused attention (p = .027) and open monitoring (p = .041) meditation increased IED density relative to the non-meditative STL control condition, whereas no differences were observed relative to the CMM control condition. Although both meditation conditions produced numerically comparable IED increases relative to STL control at the individual level, there was notable inter-individual variability depending on type of meditation. Subjects overall reported higher meditation depth scores during meditation than the STL control, and perceived depth increased with progressive meditative levels. Crucially, the relationship between IED density and perceived meditation depth changed across levels (p < .01), suggesting a dynamic interplay between neural excitability in the context of epilepsy and the subjective ease of meditative engagement. SIGNIFICANCE: This exploratory study provides direct intracranial evidence that meditation modulates interictal epileptiform activity in meditation-naïve epilepsy patients. Increased IED density during meditation suggests that these internally directed cognitive states can transiently influence epileptic network dynamics. These preliminary findings indicate a functional coupling between meditative states and cortical excitability in epilepsy, offering crucial insights into the clinical relevance of meditation in epilepsy.
Multidomain neuropsychiatric outcomes after epilepsy surgery: A systematic review and meta-analysis of depression, psychosis, cognition, and psychosocial adjustment.
Ranpariya M, Kaur G, Schwandt A … +5 more , Farooq O, Ludwig A, Shallwani H, Glover R, Li P
Epilepsia · 2026 Jun · PMID 42287176 · Publisher ↗
OBJECTIVE: To systematically evaluate neuropsychiatric outcomes-depression, anxiety, psychosis, cognition, quality of life, and psychosocial adjustment-following epilepsy surgery in adults, and to quantify pooled effect...
OBJECTIVE: To systematically evaluate neuropsychiatric outcomes-depression, anxiety, psychosis, cognition, quality of life, and psychosocial adjustment-following epilepsy surgery in adults, and to quantify pooled effect sizes. METHODS: We searched MEDLINE, Embase, PsycINFO, and the Cochrane Library from inception through December 2024, Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA 2020). Eligible cohort studies (prospective or retrospective) reported standardized neuropsychiatric outcomes in adults undergoing epilepsy surgery with ≥3 month follow-up. Random-effects meta-analyses (DerSimonian-Laird) pooled continuous outcomes as Hedges' g and dichotomous outcomes as proportions (Freeman-Tukey transformation). Heterogeneity (I) was explored via pre-specified subgroups by seizure outcome, follow-up (<2 vs ≥2 years), and instrument. Publication bias was assessed by funnel plots and Egger's and Begg's tests, and risk of bias by the Newcastle-Ottawa Scale. RESULTS: Forty-two studies (n = 6218) met the inclusion criteria; 26 contributed to quantitative meta-analyses. Pooled depression improvement was small-to-moderate (Standardized Mean Difference (SMD) = -.24; 95% confidence interval [CI] -.34 to -.14; k = 12; I = 30.5%), with larger effects in seizure-free patients (-.47; -.65 to -.29) and no significant change with persistent seizures (-.08; -.28 to .12). De novo psychiatric disorders occurred in 16.3% (95% CI: 11.4-21.8%), most commonly depression (9.8%), anxiety (7.1%), and psychosis (2.7%). Epilepsy-related psychoses decreased from 17.5% preoperatively to 4.2% postoperatively. Verbal memory decline occurred in 17%-37% of temporal lobe surgery patients but did not independently affect quality of life when seizure freedom was achieved; 20% of seizure-free left TLE patients demonstrated verbal memory improvement. Quality of life improved continuously over 5 years in seizure-free patients. Neither the Egger's (p = .86) nor Begg's (p = .84) test indicated publication bias. SIGNIFICANCE: Epilepsy surgery produces measurable improvements in depression, psychosis, and quality of life, with seizure freedom as the primary determinant. De novo psychiatric disorders in a substantial minority underscore the need for presurgical screening and longitudinal postoperative monitoring. By integrating evidence across five outcome domains-including psychosocial adjustment, not quantitatively synthesized in prior reviews-this meta-analysis offers a comprehensive framework for informed surgical counseling.
Fully automated three-dimensional deep learning-based magnetic resonance imaging segmentation of brain cavities in epilepsy surgery.
Casseb RF, de Campos BM, Loos WS … +10 more , Barbosa MER, Alvim MKM, Paulino GCL, Ghizoni E, Pucci F, Worrell S, Yassuda CL, de Souza RM, Jehi L, Cendes F
Epilepsia · 2026 Jun · PMID 42284022 · Publisher ↗
OBJECTIVE: There are several clinical and research applications for determining the amount of brain tissue resected after epilepsy surgery; however, manual segmentation of postoperative magnetic resonance imaging (MRI) i...
OBJECTIVE: There are several clinical and research applications for determining the amount of brain tissue resected after epilepsy surgery; however, manual segmentation of postoperative magnetic resonance imaging (MRI) is imprecise and time-consuming. In this study, we developed and benchmarked ResectVol DL, a freely available deep learning-based tool that performs this task automatically. METHODS: To create ResectVol DL, we trained a UNet-like deep learning model using postoperative T1-weighted MRI from epilepsy surgery patients and evaluated it against manual delineations (ground truth). ResectVol DL was also compared with three automated methods (ResectVol 1.1.2, DeepResection, and Auto3DSeg) using Dice similarity coefficient (DSC), Pearson correlation coefficient, and relative volume difference from manual segmentation. To assess false-positive detections and generalizability beyond epilepsy, we additionally processed images from healthy controls (no resection) and brain tumor cases. RESULTS: The final epilepsy cohort comprised 120 patients (57 women, mean age at surgery = 31.5 ± 15.9 [SD] years), split into training (n = 72) and test (n = 48) sets. An additional 42 images (22 healthy controls and 20 brain tumor cases) were included to test for false positives and generalizability. Segmentation performance differed across methods (Friedman test, p < .001). ResectVol Dl achieved the highest median DSC (.925), significantly outperforming ResectVol 1.1.2, DeepResection, and Auto3DSeg after Bonferroni correction. Volume-based metrics were similar for Auto3DSeg and ResectVol DL (r = .988, relative difference = 8.4% vs. r = .985, 8.1%; no significant difference), yet Auto3DSeg produced three false-positive cavities in no-surgery controls (3/22, 95% confidence interval [CI] = 3%-35%), whereas none was observed for ResectVol DL and DeepResection (0/22, 95% CI = 0%-15%). SIGNIFICANCE: ResectVol DL provides accurate, fully automated segmentation of postoperative resection cavities, offering a robust and reproducible methodological tool for large-scale postoperative imaging studies in epilepsy surgery. ResectVol DL also provides volumetric information derived from region labeling, which may serve as potential input for predictive models associated with surgery outcome; however, this application has not yet been validated.
Bridging the outcome documentation gap in epilepsy surgery: Validating large language model agents for automated Engel and International League Against Epilepsy scoring from clinical notes.
Adelson PD, Delaney H, D'Haese PF
Epilepsia · 2026 Jun · PMID 42284021 · Publisher ↗
OBJECTIVE: Timely and accurate classification of postepilepsy surgery outcomes using Engel and International League Against Epilepsy (ILAE) scales is essential for clinical follow-up, yet electronic health record documen...
OBJECTIVE: Timely and accurate classification of postepilepsy surgery outcomes using Engel and International League Against Epilepsy (ILAE) scales is essential for clinical follow-up, yet electronic health record documentation often lacks the structured detail needed for reliable scoring. This study aimed to validate large language model (LLM) agents for autonomous extraction of standardized postsurgical outcomes from unstructured follow-up notes. METHODS: We performed a retrospective validation study of deidentified postoperative epilepsy follow-up notes from patients who underwent epilepsy-related surgery or neuromodulation between 2000 and 2025 (n = 170). Each note was processed once with two fixed GPT-4-turbo prompt configurations: a concise definition-based prompt and a context-aware prompt incorporating temporal, causal, and adherence logic. Human-adjudicated consensus served as the reference standard. Prespecified metrics included exact score agreement, clinically adjacent agreement, ordinal distance, Wilson 95% confidence intervals (CIs), and paired tests comparing prompt configurations. RESULTS: Valid follow-up intervals were available for 170 cases; the median time from surgery to analyzed note was 32.7 months (interquartile range = 9.6-97.9). Human reviewers achieved 91.2% raw agreement for Engel major class (Cohen kappa = .86, 95% bootstrap CI = .79-.92) and 83.5% raw agreement for ILAE category (quadratic weighted kappa = .93, 95% CI = .89-.96). The definition-based prompt achieved 56.5% exact Engel subclass agreement (95% CI = 49.0-63.7) and 60.6% exact ILAE agreement (95% CI = 53.1-67.6). The context-aware prompt improved exact agreement to 94.7% for Engel (95% CI = 90.2-97.2) and 93.5% for ILAE (95% CI = 88.8-96.3), with lower ordinal distance for both scales (paired sign tests p < .001). SIGNIFICANCE: The meaningful finding is not that a general LLM can recite outcome definitions, but that a context-aware LLM agent can apply seizure-outcome logic to heterogeneous real-world notes with high agreement against adjudicated human consensus. Definition-only prompting remained unreliable in nuanced categories, supporting the need for explicit clinical reasoning structure, auditability, and privacy-preserving deployment.
Magnetic resonance imaging-based ranking of resection-related cortical candidates for presurgical localization in epilepsy using a prior-aware graph attention transformer.
Yao C, Yu Y, Shan Y … +4 more , Cui B, Zhang S, Li J, Lu J
Epilepsia · 2026 Jun · PMID 42283780 · Publisher ↗
OBJECTIVE: Structural magnetic resonance imaging (MRI) is fundamental to presurgical localization in epilepsy, but subtle epilepsy-related abnormalities may not always be apparent on routine review. This study aimed to d...
OBJECTIVE: Structural magnetic resonance imaging (MRI) is fundamental to presurgical localization in epilepsy, but subtle epilepsy-related abnormalities may not always be apparent on routine review. This study aimed to develop and externally validate an MRI-only graph attention transformer for ranking resection-related cortical candidates and to evaluate its reader-level utility. METHODS: Graph Attention Transformer for Epilepsy-Related Candidate Zones (GATEZ) was developed using preoperative three-dimensional T1-weighted MRI from the publicly released IDEAS (Imaging Database for Epilepsy and Surgery) database. Participants with a 12-month International League Against Epilepsy class 1 outcome were split into training, validation, and internal test sets (n = 171/37/37). Each participant was represented as a 1000-parcel cortical graph with five regional morphometric features and an individualized Morphometric Inverse Divergence network; postoperative resection masks served as the surgical reference standard for model supervision. External validation used 183 consecutive surgical participants with epilepsy who underwent hybrid F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/MRI, with MRI only used for model inference. Reader-level utility was evaluated in a blinded three-reader study comparing MRI alone, MRI plus F-FDG PET, and MRI plus GATEZ. RESULTS: In the internal test cohort, GATEZ placed at least one resection-overlapping parcel within the Top-10 ranked candidates in 92% of participants, with a mean Top-10 positive predictive value of 62%. Performance remained stable in the independent external cohort, with an 87% Top-10 hit rate and 59% mean Top-10 positive predictive value. Node-level area under the precision-recall curve was .29 internally and .27 externally, indicating stable enrichment of resection-related regions among the highest ranked candidates. In the blinded reader study, MRI + GATEZ improved detection compared with MRI alone (74%-78% vs. 58%-66% across readers; adjusted p ≤ .001 for all readers) and performed similarly to MRI + FDG (78%-80% across readers; adjusted p ≥ .34 for all readers). SIGNIFICANCE: GATEZ generates a concise Top-K shortlist of resection-related cortical candidates and may serve as a practical second-look aid for presurgical localization.
Diagnosis and management guidelines for infantile epileptic spasms syndrome around the world: A scoping review and comparative study of international approaches.
Erdemir G, Rao CK, Pino AF … +19 more , Briscoe C, Samanta D, Wilmshurst JM, Bhatia S, Carpenter JL, Hoei-Hansen C, Jain P, Stodberg T, Whitney R, Matsuura R, Astorga KR, Gallinato KA, Singhi P, Hadijinicolaou A, Melikishvili G, Smeyers P, Specchio N, Auvin S, Pediatric Epilepsy Research Consortium Infantile Spasm Work Group and International Committee
Epilepsia · 2026 Jun · PMID 42274306 · Publisher ↗
OBJECTIVE: Infantile epileptic spasms syndrome (IESS) is an epileptic encephalopathy requiring rapid diagnosis and treatment to optimize neurodevelopmental outcomes. Although multiple national and regional guidelines exi...
OBJECTIVE: Infantile epileptic spasms syndrome (IESS) is an epileptic encephalopathy requiring rapid diagnosis and treatment to optimize neurodevelopmental outcomes. Although multiple national and regional guidelines exist, recommendations vary. We conducted a comparative scoping review of international IESS guidelines to synthesize current recommendations, evaluate trends, and examine regional differences in diagnosis and treatment. METHODS: Published guidelines were identified through MEDLINE, Embase, and Cochrane CENTRAL, using PRISMA-ScR (Preferred Reporting Items of Systematic Reviews and Meta-Analyses, extension for scoping reviews) methodology and PROSPERO (Prospective Register of Systematic Reviews) registration. Unpublished institutional protocols were obtained from pediatric neurologists worldwide. Extracted variables included diagnostic evaluation, treatment recommendations, dosing, response assessment, and monitoring. Descriptive analysis compared recommendations across regions and time periods. RESULTS: Twenty-eight guidelines were analyzed (16 published, 12 unpublished), including 15 from high-income countries (HICs) and 11 from low- and middle-income countries (LMICs). Electroencephalography was recommended in nearly all guidelines (27/28, 96%), whereas brain magnetic resonance imaging (20/28, 71%) and genetic testing (15/28, 54%) were less consistent. Vigabatrin was universally recommended as first-line therapy for IESS-associated tuberous sclerosis complex. Earlier guidelines (2004-2015) favored adrenocorticotropic hormone (ACTH), whereas recent guidelines (2016-2024) increasingly endorsed prednisolone and vigabatrin. Combination therapy emerged after 2017 (~25%). LMIC guidelines uniformly recommended prednisolone, whereas HIC guidelines more frequently endorsed ACTH, vigabatrin, and combination therapy. Treatment response was most often assessed at ~14 days. SIGNIFICANCE: International IESS guidelines share core principles but demonstrate evolving practices and persistent global disparities. HIC and LMIC recommendation differences likely reflect variation in medication access, cost, and diagnostic resources. Harmonized international guidance may reduce disparities and improve equitable care. Further research is needed to develop standardized treatment protocols and explore novel therapeutic options to optimize outcomes for infants with IESS.
Pediatric epilepsy surgery: Global survey of invasive explorations.
Ramantani G, Feucht M, Cserpan D … +48 more , Aparicio J, Arzimanoglou A, Bartolomei F, Bingaman W, Braun KPJ, Burman RJ, Cao D, Caraballo R, Chipaux-Raffo M, Cloppenborg T, Cross JH, Cukiert A, Cukiert CM, Curry DJ, De Palma L, Dimova P, Eltze C, Englot DJ, Nico Enslin JM, Fallah A, Francione S, Gill D, Hallböök T, Harvey AS, Holthausen H, Jayalakshmi S, Jiang Y, Kannan L, Lallas M, Patil SB, Pérez-Jiménez MÁ, Pérez-Poveda JC, Pieper T, Rona S, San Antonio-Arce V, Shetty J, Smith ML, Suwanpakdee P, Tarta Arsene O, Tassi L, Tisdall M, Tripathi M, Naduvil Valappil AM, Weiner H, Wirrell E, Cai L, Ferrand-Sorbets S, ILAE Pediatric Epilepsy Surgery Taskforce and Study Group
Epilepsia · 2026 Jun · PMID 42274288 · Publisher ↗
OBJECTIVE: Invasive presurgical evaluation plays a key role in pediatric epilepsy surgery, particularly in magnetic resonance imaging (MRI)-negative cases, by guiding resective, disconnective, or ablative procedures. Thi...
OBJECTIVE: Invasive presurgical evaluation plays a key role in pediatric epilepsy surgery, particularly in magnetic resonance imaging (MRI)-negative cases, by guiding resective, disconnective, or ablative procedures. This International League Against Epilepsy (ILAE) Pediatric Epilepsy Surgery Taskforce study provides an updated global overview of current invasive evaluation practices. METHODS: Group-level data were collected from 61 epilepsy surgery programs (49 pediatric-only) in 29 countries across six continents. Included were children and adolescents who underwent presurgical evaluation and epilepsy surgery in 2023. The study was designed to enable comparison with the similar ILAE survey conducted in 2004. RESULTS: A total of 2427 patients were included. Invasive evaluations were performed in 21.1% of cases, most frequently in North America (33.7%, higher than Europe: 18.0%, p = .003). Among invasive cases, 32.3% had no detectable MRI abnormalities. The main indication for invasive evaluation was seizure onset localization (88.1%), followed by motor or sensory mapping (17.2%) and language mapping (14.2%). Stereoelectroencephalography (SEEG) was the predominant technique (19.8% overall, 93.6% of invasive cases), more common in North America (30.0%, p = .021) and less common in South America (7.4%, p < .001). Subdural electrodes were used in only 3.2% of invasive cases, and combined depth and subdural approaches in 3.2%. SEEG-guided radiofrequency thermocoagulation (RF-TC) was performed in 40.9% of SEEG cases, most commonly in Asia (63.8%). In 16.2% of invasive evaluations, patients did not proceed to resection, disconnection, or ablation, with the highest rate in Europe (28.5%). SIGNIFICANCE: This global survey provides the first broad overview of invasive evaluation practices in pediatric epilepsy surgery across participating centers worldwide. It highlights the widespread adoption of SEEG, declining use of subdural electrodes, and increasing application of SEEG-guided RF-TC. The high proportion of MRI-negative cases and the considerable proportion of patients not proceeding to resection, disconnection, or ablation underscore the complexity of contemporary surgical candidates and the need for further refinement of selection strategies.
Seizure relapse in new onset epilepsy: It is not always drug resistance.
Catania C, Menetre E, Fitsiori A … +9 more , Kurz FT, Moreno Legast G, Vulliemoz S, Genoud M, Mégevand P, Wiest R, Picard F, Beniczky S, Seeck M
Epilepsia · 2026 Jun · PMID 42274285 · Publisher ↗
OBJECTIVE: Seizure recurrence in new onset epilepsy (NOE) can result from various factors. Although drug ineffectiveness is frequently investigated, other causes-such as nonadherence, inadequate treatment, nonepileptic e...
OBJECTIVE: Seizure recurrence in new onset epilepsy (NOE) can result from various factors. Although drug ineffectiveness is frequently investigated, other causes-such as nonadherence, inadequate treatment, nonepileptic events (e.g., functional/dissociative), or acute symptomatic seizures-also impact patient outcomes. This retrospective, longitudinal single-center study evaluated relapse causes over a 5-year period in a cohort of NOE patients. METHODS: We reviewed the NOE registry of Geneva University Hospital, including adult patients diagnosed between 2005 and 2019. Of 740 consecutive patients, 330 with more than 5 years of follow-up were included in the analysis. Relapses after antiseizure medication (ASM) initiation were classified into seven categories: poor adherence, inadequate treatment, ineffective treatment, acute symptomatic seizures, nonepileptic seizures, multiple, and unknown causes. Mixed-effects logistic regression and post hoc analyses were used to assess temporal trends. RESULTS: A total of 202 of 330 patients (61%) experienced at least one relapse; 181 occurred after ASM initiation. Of these, 32% (57/181) were due to treatment ineffectiveness, whereas 68% were attributable to other causes. Inadequate treatment was the most frequent cause in year 1 (37%) but declined to 10% by year 5 (p < .001). Poor adherence remained stable (27%-38%). The proportion of drug ineffectiveness as a cause of relapse increased over time (22% in year 1 to 41% in year 5). Drug-resistant epilepsy (DRE) was diagnosed in 7% of the entire cohort. Generalized tonic-clonic (GTC) seizures at relapse were associated with poor adherence, whereas non-GTC seizures were linked to ineffectiveness (p < .001). SIGNIFICANCE: In our cohort, most early relapses in NOE were due to modifiable factors. Systematic identification of relapse causes can prevent misclassification of DRE and reduce unnecessary treatment escalation. The high proportion of patients lost to follow-up is a relevant limitation of this study; however, a substantial selection bias is unlikely.
The dynamic functional connectivity peak index: Detection of interictal epileptic activity with fMRI.
Sainburg LE, Roche A, Makhoul GS … +7 more , Rogers BP, Roberson SW, Meletti S, Vaudano AE, Chang C, Englot DJ, Morgan VL
Epilepsia · 2026 Jun · PMID 42274280 · Publisher ↗
OBJECTIVE: Epileptogenic zone (EZ) localization is crucial for surgical treatment of patients with medication-resistant epilepsy. Although simultaneous electroencephalography (EEG) and functional magnetic resonance imagi...
OBJECTIVE: Epileptogenic zone (EZ) localization is crucial for surgical treatment of patients with medication-resistant epilepsy. Although simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) can detect interictal discharges for EZ localization, clinical adoption is limited by the need for specialized equipment and expertise. Prior EEG-fMRI work has shown that interictal discharges produce fMRI activation in the EZ and deactivation in the default mode network. Here we use dynamic functional connectivity (dFC) to detect these opposing activations and localize potential interictal activity using fMRI without simultaneous EEG in a cohort composed primarily of temporal lobe epilepsy (TLE). METHODS: We quantified dFC with the edge timeseries approach and present examples of negative dynamic functional connectivity peaks following interictal discharges in two patients with TLE who received simultaneous EEG-fMRI. We defined the rate of these peaks as the "dFC peak index," hypothesizing it to be elevated in epileptic tissue. We assessed this hypothesis in 62 medication-resistant patients with focal epilepsy who underwent fMRI without simultaneous EEG (49 unilateral temporal, 11 bilateral temporal, 1 frontal, and 1 parietal). We Z-scored dFC peak index in each patient to healthy controls (n = 109) to identify regions with abnormally high values and tested whether these aligned with patients' EZs or correlated with clinical parameters. RESULTS: The dFC peak index was elevated in epileptic medial temporal structures in patients with TLE (p <.05). Resection of regions with higher values correlated with better seizure outcomes after surgery (area under the curve [AUC] = .80, p = .0002), even in patients without hippocampal lesions on MRI (AUC = .79, p = .04). SIGNIFICANCE: This study presents the dFC peak index, which aims to detect interictal epileptic activity using fMRI without simultaneous EEG. Our results indicate that this measure is elevated in epileptic tissue in TLE, suggesting that it could provide unique information to guide epilepsy surgery.
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