Epilepsia[JOURNAL]
Sun
200 papers
Serum NfL, GFAP, and p-tau217 in adults with drug-resistant epilepsy and intellectual disabilities: Signs of ongoing neural injury.
Kwetsie H, Verberk IMW, van Ool JS … +8 more , Rampen AJJ, Rousset RZ, Wolf NI, Maes-Festen DAM, van Karnebeek CDM, Teunissen CE, Boot E, van Eeghen AM
Epilepsia · 2026 Mar · PMID 41910248 · Publisher ↗
OBJECTIVE: Adults with epilepsy and intellectual disabilities (IDs) may be at increased risk of dementia, but clinical evaluation is complex and use of conventional biomarkers is often considered too invasive. We explore...
OBJECTIVE: Adults with epilepsy and intellectual disabilities (IDs) may be at increased risk of dementia, but clinical evaluation is complex and use of conventional biomarkers is often considered too invasive. We explored abnormality of serum neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau-217 (p-tau217) in these adults, and their associations with clinical outcomes. METHODS: Serum biomarker levels were quantified with Single Molecule Array (Simoa) in 68 adults with co-occurring epilepsy and ID at a median age of 52.0 (range 24-76) years. Levels were classified normal/abnormal (>95th percentile) in comparison to reference data of age-matched healthy controls (NfL, GFAP) or Alzheimer's disease (AD)-specific cutoff (p-tau217). Associations with age were assessed with correlations and segmented regression analyses. Associations with adaptive decline, suspected dementia, ID, epilepsy, antiseizure medication, comorbidity, and mortality were explored using chi-square tests, Mann-Whitney U tests, log rank tests, and Cox regression analyses. RESULTS: NfL levels were abnormal in 51.5%, GFAP in 63.2%, and p-tau217 in 2.9%. Age-corrected Z-scores of NfL were still significantly associated with age (r = .31, p = .01). Elevated NfL was associated with significant adaptive decline (χ = 7.20, p = .007), suspected dementia (χ = 10.73, p = .001), monthly seizure frequency (χ = 5.21, p = .03), non-early seizure onset (U = 281, p < .001), carbamazepine use (χ = 4.38, p = .04), and mortality (Log rank p = .04; hazard ratio [HR] p = .007). GFAP levels were significantly higher in severe ID (median Z = 2.5) compared to mild ID (median Z = 1.6) (U = 196, p = .02). Having abnormal levels of GFAP and NfL simultaneously was the most common biomarker profile in participants with suspected dementia (69.2%). SIGNIFICANCE: NfL and GFAP were abnormal in many participants, coinciding with clinical decline. Findings are suggestive for ongoing neural injury, but not necessarily for AD.
Mental health impacts experienced by caregivers of people with Dravet syndrome: A systematic literature review.
Strzelczyk A, Meskis MA, Wilson G … +6 more , Jacob B, Helmstaedter C, von Gaudecker J, Hood V, Hughes C, Perry MS
Epilepsia · 2026 Jun · PMID 41910243 · Full text
OBJECTIVE: Dravet syndrome (DS) places tremendous burden on caregivers owing to the extent of required assistance and impact on daily living, as well as the risk to the individual with DS of premature mortality from sudd...
OBJECTIVE: Dravet syndrome (DS) places tremendous burden on caregivers owing to the extent of required assistance and impact on daily living, as well as the risk to the individual with DS of premature mortality from sudden unexpected death in epilepsy and morbidity associated with nonseizure manifestations. This systematic literature review provides an up-to-date characterization of the mental health impacts experienced by caregivers of people with DS. METHODS: Databases (1974 to August 29, 2024 in Embase; 1946 to August 29, 2024 in MEDLINE) were searched for records containing keywords relevant to mental health in caregivers of people with DS. The study population comprised caregivers of people with DS with any or no intervention and/or comparator (and excluding pharmacologic interventions affecting caregiver burden-related outcomes) and with mental health outcomes that included depression, anxiety, fatigue, sleep quality, stress, mood, and quality of life scales. RESULTS: Database searches returned 519 records; 20 published articles were included. Most common were cross-sectional studies, with populations from Asia, Australia, Central/South America, Europe, and North America. Study sample sizes ranged from seven to 256 caregivers of people with DS; most caregivers were female. Depression and anxiety were reported in 11 and 10 articles, respectively; the prevalence of depression and anxiety among caregivers ranged 5%-66% and 5.2%-80%, respectively. Some studies used instruments to assess mental health outcomes; Beck Depression Inventory-II for depressive symptoms and the Hospital Anxiety and Depression Scale for symptoms of anxiety and depression were reported in three and two articles, respectively. Factors potentially associated with mental health including sleep quality, fatigue, and stress were commonly reported, with poor sleep quality and fatigue often linked to nighttime monitoring of people with DS. SIGNIFICANCE: Physicians should routinely assess the mental health of caregivers of people with DS; future studies should focus on identifying interventions that ease burden on caregivers.
Ranking of antiseizure medications in a panel of focal seizure models predicts their comparative efficacy in clinical add-on trials in drug-resistant focal epilepsy.
Löscher W, Klein P
Epilepsia · 2026 Mar · PMID 41902701 · Publisher ↗
OBJECTIVE: Most antiseizure medications (ASMs) have been discovered by testing in animal models, which are generally thought to predict antiseizure activity in patients. However, it is not known whether any of these mode...
OBJECTIVE: Most antiseizure medications (ASMs) have been discovered by testing in animal models, which are generally thought to predict antiseizure activity in patients. However, it is not known whether any of these models (or a combination of models) can predict whether a novel ASM exhibits higher clinical efficacy in focal drug-resistant epilepsy (DRE) than benchmark ASMs such as carbamazepine or levetiracetam. This important question has plagued epilepsy drug discovery for over three decades and serves as the basis of the present analysis. METHODS: The present analysis includes 23 ASMs that the U.S. Food and Drug Administration (FDA) approved for the treatment of focal-onset seizures. For assessing comparative preclinical activity, we used the median effective dose (ED) determined in six rodent models of induced generalized or focal-onset seizures. For assessing comparative clinical efficacy, seizure-freedom rates recorded during add-on treatment in randomized controlled clinical trials in patients with focal DRE were used. The preclinical ED were ranked from most potent to least potent by SUCRA (surface under the cumulative ranking curve). Correlation analysis of preclinical and clinical data was used to determine the predictive validity of the animal models. RESULTS: Except for the pilocarpine model, none of the seizure models predicted the comparative efficacy of add-on treatment with ASMs in focal DRE. However, when we combined the ED-based ranks from two to four models of focal-onset seizures, highly significant positive correlations with seizure-freedom rates in the clinical trials were obtained. SIGNIFICANCE: The present study shows that ranking of ASMs across a panel of mechanistically complementary but agnostic models of focal-onset seizures yields greater translational accuracy and clinical predictivity for patients with focal DRE than rankings based on any single model. This novel finding can be used when defining a path forward that best identifies the most promising investigational compounds to advance to more expensive and time-consuming clinical investigations.
Deep brain stimulation of the thalamus for intractable epilepsy (FRANCE study): A randomized clinical trial.
Chabardès S, Bartolomei F, Nica A … +28 more , Haegelen C, Minotti L, Piallat B, Mosca C, Massicot S, Rheims S, Guenot M, Cuny E, Aupy J, Maillard L, Colnat-Coulbois S, Leroy C, Carron R, Coubes P, Gélisse P, Karachi C, Navarro V, Devaux B, Chassoux F, Derambure P, Reyns N, Sol JC, Valton L, Fontaine D, Bourg V, Kahane P, David-Tchouda S, Regis J
Epilepsia · 2026 Mar · PMID 41902639 · Publisher ↗
OBJECTIVE: This study was undertaken to evaluate the efficacy and safety of deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) compared with best medical treatment (BMT) in patients with drug-resi...
OBJECTIVE: This study was undertaken to evaluate the efficacy and safety of deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) compared with best medical treatment (BMT) in patients with drug-resistant epilepsy (DRE). METHODS: This randomized, open-label, phase 3 controlled trial was conducted across 14 specialized epilepsy and DBS centers. Eligible participants were adults with focal or multifocal DRE who had previously failed vagus nerve stimulation (VNS). Sixty-one patients were randomized 1:1 either to receive continuous bilateral ANT-DBS (n = 30) or to continue BMT, including VNS (n = 31), for 12 months. Afterward, patients in the BMT group were offered delayed ANT-DBS and followed for an additional year. The primary outcome was the change in monthly severe seizure frequency (defined on the modified Chalfont Scale) at 12 months. Safety outcomes were also recorded. RESULTS: Among 67 screened patients, 61 were enrolled. At 12 months, median seizure reduction was greater in the DBS group (-44%, interquartile range [IQR] = -67 to 0) versus the BMT group (-6%, IQR = -56 to 20; p = .09); 44.5% of patients in the DBS group achieved a ≥50% reduction in seizure frequency compared to 27% in the BMT group. Within-group analyses showed significant seizure reductions in the DBS group at both 12 months (-44%, p < .001) and 24 months (-46%, p < .001), as well as in the delayed DBS group at 12 months (-36%, IQR = -73 to -4; p < .001). No significant differences in quality of life were observed between groups, and no major DBS-related adverse events were reported. SIGNIFICANCE: Our study suggests a potential benefit rather than demonstrating superiority of ANT-DBS over medical therapy. However, within-group improvements and favorable safety profile support the use of ANT-DBS as a palliative treatment option in patients with DRE who have failed VNS.
Recommendations for structural magnetic resonance imaging in infants with first afebrile seizure or new onset epilepsy: Evidence-based recommendations from the ILAE Neuroimaging Task Force.
Winston GP, Salemme S, Cantalupo G … +13 more , Cendes F, D Arco F, Federico P, Gaillard WD, Kobayashi E, Novotny EJ, Ogbole G, Pullattayil AK, Tortora D, Whitehead MT, Yi T, Brigo F, Vaudano AE
Epilepsia · 2026 Jun · PMID 41894169 · Full text
Infants aged 1-24 months with new onset epilepsy frequently present with structural brain abnormalities, yet no updated evidence-based magnetic resonance imaging (MRI) guidelines exist for this population. The Internatio...
Infants aged 1-24 months with new onset epilepsy frequently present with structural brain abnormalities, yet no updated evidence-based magnetic resonance imaging (MRI) guidelines exist for this population. The International League Against Epilepsy (ILAE) Neuroimaging Task Force developed evidence-based recommendations for structural brain MRI in infants with a first afebrile seizure or new onset epilepsy. A multidisciplinary panel defined three PICO (patients, intervention, comparison group, outcome under consideration) questions, conducted a systematic review (PROSPERO [Prospective Register of Systematic Reviews] CRD42024592653), and reported the results in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. Risk of bias was evaluated using the JBI (Joanna Briggs Institute) checklist. GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology was used to assess certainty of evidence and formulate recommendations for the following: (1) the effectiveness of MRI in identifying underlying etiologies, (2) clinical predictors of MRI abnormalities, and (3) MRI protocols. Seventeen studies (n = 1209) were included. Among 753 infants who underwent MRI, 438 (58.2%) had abnormal findings. Despite heterogeneity in MRI protocols and reporting, the evidence supports the utility of MRI in this population. Specific clinical features (focal seizure semiology, abnormal neurological examination, seizure duration > 5 min, focal electroencephalographic abnormalities, developmental delay, and perinatal complications) were associated with abnormal MRI findings, although methodological limitations reduce certainty. Only six studies provided data on MRI sequences; however, none reported findings specifically in relation to the diagnostic accuracy or yield of individual protocols, precluding the development of evidence-based recommendations on MRI protocol selection. MRI is conditionally recommended in all infants with a first afebrile seizure or new onset epilepsy. MRI could be prioritized in those with specific clinical features indicative of higher likelihood of abnormal findings. Recommendations are based on very low certainty of evidence. These are the first ILAE-endorsed, evidence-based recommendations for MRI in infants with first afebrile seizure or new onset epilepsy. Further prospective studies with standardized protocols are needed to refine MRI indications and optimize diagnostic yield in this age group.
A phase 3, randomized clinical trial of soticlestat as adjunctive therapy for Lennox-Gastaut syndrome.
Guerrini R, Marsh ED, Liao WP … +13 more , Imai K, Kravljanac R, Altmann A, Hahn CD, Auvin S, Schiemann J, Khan Y, Mitra P, Sheikh SI, von Rosenstiel P, Asgharnejad M, Dlugos D, Murthy V
Epilepsia · 2026 Mar · PMID 41891667 · Publisher ↗
OBJECTIVE: There remains a need for new treatments for Lennox-Gastaut syndrome (LGS), a developmental and epileptic encephalopathy with a heterogenous patient population that often requires polytherapy. The phase 3, rand...
OBJECTIVE: There remains a need for new treatments for Lennox-Gastaut syndrome (LGS), a developmental and epileptic encephalopathy with a heterogenous patient population that often requires polytherapy. The phase 3, randomized SKYWAY study (NCT04938427) investigated the efficacy and safety of the cholesterol 24-hydroxylase inhibitor soticlestat (TAK-935) in participants with LGS. METHODS: This global, double-blind, placebo-controlled trial enrolled participants aged 2-55 years with LGS (adjudicated by the Epilepsy Study Consortium). Participants were randomized 1:1 to stable background medication plus either soticlestat (≤300 mg twice daily, weight-adjusted) or placebo over 16 weeks (4-week titration plus 12-week maintenance). The primary endpoint was percentage change from baseline in major motor drop (MMD) seizure frequency per 28 days. RESULTS: SKYWAY enrolled 270 participants (placebo, n = 136; soticlestat, n = 134); mean age was 12.9 years; 95% were receiving ≥2 antiseizure medications. The difference in median change from baseline in MMD seizure frequency for soticlestat versus placebo was -1.17% (p = .785) during the full treatment period and 2.43% (p = .778) during maintenance. No meaningful difference was observed between soticlestat and placebo for most key secondary endpoints; numerical trends for small effects favoring soticlestat were seen in the proportions of participants showing improvement in the Clinical Global Impression of Improvement (CGI-I) Non-seizure Symptoms Disruptive Behaviors domain (odds ratio = 1.91, nominal p = .032) and CGI-I Seizure Intensity and Duration (odds ratio = 1.67, nominal p = .029). Treatment-related adverse events (TEAEs; mostly mild or moderate) were reported in 68.4% of placebo-treated and 74.6% of soticlestat-treated participants; the most frequent treatment-related TEAE with soticlestat was somnolence. Serious treatment-related TEAEs occurred in one placebo-treated and three soticlestat-treated participants. SIGNIFICANCE: Soticlestat did not demonstrate efficacy versus placebo in reducing MMD seizure frequency; the safety findings were consistent with those of previous studies. These data suggest that targeting cholesterol 24-hydroxylase is not a suitable pharmacotherapeutic strategy for LGS.
Delayed and deferred surgery associated with cenobamate use in people with drug-resistant focal epilepsy.
Pellinen J, Sillau S, Bui A … +6 more , Danciutiu A, Kaye L, Sood A, Ferrari L, Rosenfeld WE, Elder C
Epilepsia · 2026 Mar · PMID 41885758 · Publisher ↗
OBJECTIVE: Cenobamate has been shown to be an effective antiseizure medication for some patients with drug-resistant focal epilepsy being considered for epilepsy surgery. This retrospective single-center study evaluated...
OBJECTIVE: Cenobamate has been shown to be an effective antiseizure medication for some patients with drug-resistant focal epilepsy being considered for epilepsy surgery. This retrospective single-center study evaluated whether surgery was obtained within 12 months for patients who received cenobamate as a treatment during the presurgical evaluation and those who did not, comparing across years before and after cenobamate approval. METHODS: Patients undergoing surgical evaluation for drug-resistant focal epilepsy at the University of Colorado during 2018 and 2023 who had 12 months of follow-up data were analyzed. Comparison years were also chosen to avoid the confounding effect of the COVID-19 pandemic on surgical volume (2020-2021). This allowed for comparison times before and after cenobamate's US Food and Drug Administration approval. The primary outcome (surgery within 12 months) was modeled with potential explanatory variables using multiple logistic regression. A p-value of <.05 was considered significant. RESULTS: After controlling for potentially confounding clinical and demographic variables, cenobamate use during the presurgical evaluation period was associated with .13 lower odds of surgery within 12 months compared to not being prescribed this medication (95% confidence interval [CI] = .04-.42, p < .001). Being Hispanic or Latino was significantly associated with .23 lower odds of surgery within 12 months compared to patients who did not report being Hispanic or Latino (95% CI = .09-.61, p = .003). Year of evaluation (2023 vs. 2018), education level, age, and sex did not have significant associations with undergoing surgery within 12 months. SIGNIFICANCE: Patients with drug-resistant focal epilepsy undergoing evaluation for epilepsy surgery may benefit from cenobamate. In this study, patients who received cenobamate during the presurgical evaluation were less likely to undergo surgery within 12 months. The delay to surgery identified among Hispanic and Latino patients suggests potential barriers to care in this patient population warranting further investigation.
Intracranial electroencephalographic approaches in the intensive care unit: Safety, feasibility, and coverage.
Smeijers S, Segreti M, Van Hoylandt A … +5 more , Gijs J, van Loon J, Scheldeman L, Depreitere B, Theys T
Epilepsia · 2026 Mar · PMID 41885732 · Publisher ↗
OBJECTIVE: Nonconvulsive epileptic activity is common after acute brain injury and contributes to neuronal injury and poor outcomes. Although intracranial electroencephalography (iEEG) improves detection compared with su...
OBJECTIVE: Nonconvulsive epileptic activity is common after acute brain injury and contributes to neuronal injury and poor outcomes. Although intracranial electroencephalography (iEEG) improves detection compared with surface EEG (suEEG), it currently relies on focal recordings of epileptic dynamics. We prospectively evaluated multielectrode iEEG strategies designed to achieve large-scale cortical and deep brain coverage in critically ill patients. METHODS: In a prospective cohort of adults with acute brain injury requiring invasive neuromonitoring, we implemented four depth electrode-based iEEG techniques: three electrocorticographic approaches (open subdural, burr hole subdural, and foramen ovale) and one stereotactic (transcortical) approach. The primary objective was to establish and quantify the extent and durability of cortical recordings. Additional assessments included safety, feasibility, and management impact. Electrode localization was performed in MNI305 space, and recording longevity was assessed using Kaplan-Meier and Cox proportional hazards models. RESULTS: Thirty patients with severe brain injury underwent implantation of 64 electrodes (772 contacts), yielding 361 total iEEG recording days across heterogeneous etiologies and surgical settings. Multielectrode implantation enabled distributed sampling spanning multilobar frontoparietotemporal cortical clusters. Overall, 72% of electrodes sampled cortical convexity alone, whereas 28% incorporated deep targets, including mesial temporal and orbitofrontal regions. Recording durability differed by implantation strategy (log-rank p = .0002), with a mean combined iEEG-suEEG monitoring duration of 14.5 days per patient. Implantation was successful in >95% of electrodes, monitoring started within 24 h postoperatively in 88%, and the per-electrode risk of a causally related adverse event was 3.1%, without hemorrhagic complications. iEEG influenced treatment initiation or escalation in 32% of monitored patients. SIGNIFICANCE: Multielectrode iEEG strategies enable durable, large-scale cortical sampling in acute brain injury while remaining feasible and safe in the intensive care unit. By shifting from focal to distributed spatial sampling, these approaches provide a conceptual framework for improving detection of epileptic activity in critically ill patients.
Underutilization of syndrome-specific ICD-10 codes for genetic epilepsies: Implications for precision medicine.
Moura Coelho da Silva É, Brünger T, Taylor G … +13 more , Sinha M, Merket A, Cherukara A, Bajaj S, Clark J, Montanucci L, Huth EA, Fauteux M, Lhatoo SD, Boßelmann CM, Leu C, Tai RA, Lal D
Epilepsia · 2026 May · PMID 41885712 · Full text
Syndrome-specific International Classification of Diseases, 10th Revision (ICD-10) codes have the potential to improve identification of patients for precision therapies, clinical trials, and research, yet their real-wor...
Syndrome-specific International Classification of Diseases, 10th Revision (ICD-10) codes have the potential to improve identification of patients for precision therapies, clinical trials, and research, yet their real-world uptake is not well characterized. We evaluated the utilization of syndrome-specific ICD-10 codes at a large academic medical center among patients with pathogenic or likely pathogenic variants in 10 monogenic epilepsy genes with established codes (CDKL5, EHMT1, KCNQ2, MECP2, MED13L, SCN1A, SHANK3, SLC13A5, SLC2A1, SYNGAP1). Patients were identified from an institutional genetic testing database and were included if they had at least one clinical encounter after code implementation or genetic diagnosis. Variants of uncertain significance were manually curated, and Rett and Dravet phenotypes were reviewed for accuracy. Of 83 patients with qualifying variants, 39 met inclusion criteria. Only 56.4% (22/39) were ever assigned a syndrome-specific ICD-10 code, which appeared in 31.1% of encounters and accounted for 14.5% of all documented codes. Uptake varied by syndrome, provider specialty, and encounter type and increased over time. In the Dravet syndrome subgroup (n = 23), generic epilepsy codes were documented more than twice as often as the Dravet-specific code (G40.83). When G40.83 was documented, other epilepsy codes were used less frequently, suggesting it may be treated as a substitute for broader epilepsy codes. These findings demonstrate inconsistent and limited adoption of syndrome-specific ICD-10 codes, highlighting the need for improved coding support and integration of structured genetic data within the electronic health record.
Performance of the 5-SENSE score in a pediatric and young adult cohort of 100 consecutive stereoelectroencephalography cases.
Trank L, Weber ARB, Beatty C … +5 more , Brown-Mitchell G, Eisner M, Pindrik J, Shaikhouni A, Ostendorf A
Epilepsia · 2026 May · PMID 41885698 · Full text
This study assesses the validity of the 5-SENSE score in a cohort of pediatric patients with epilepsy and evaluates associations between the score, ancillary testing, and surgical outcomes. We retrospectively calculated...
This study assesses the validity of the 5-SENSE score in a cohort of pediatric patients with epilepsy and evaluates associations between the score, ancillary testing, and surgical outcomes. We retrospectively calculated the 5-SENSE score in a single-center predominantly pediatric cohort and calculated the sensitivity and specificity for predicting a non-focal stereo-electroencephalography (SEEG). In addition, we examined the relationship between score and post-surgical outcome. Finally, we evaluated the association between ancillary testing and SEEG focality. One hundred cases were included. The 5-SENSE score had a sensitivity (95% confidence interval [CI]) of 49% (35.6-62.2), specificity of 75% (63.6-85.5), and area under the curve of 0.673 (0.567-0.780). The sensitivity and specificity were similar in children 13 years or younger compared to those older than 13 years. Ancillary testing lateralized in agreement with a focal SEEG finding in 61% of patients, with sensitivity of 43% and specificity of 76% (p = 0.045). Ancillary testing confirmed the 5-SENSE score but did not significantly improve sensitivity. Higher 5-SENSE scores were associated with better Engel outcomes (p = 0.037). The 5-SENSE score performed comparably to the published adult validation cohort. Use of the 5-SENSE score in pediatric patients may improve patient selection for SEEG but is not a sole predictor of result or outcome.
Pharmacokinetic variability and complex two-way interactions with cenobamate in patients with refractory epilepsy.
Johannessen Landmark C, Belkilani H, Awad L … +4 more , Burns ML, Gottås A, Svendsen T, Sætre E
Epilepsia · 2026 Jun · PMID 41874535 · Publisher ↗
OBJECTIVES: Cenobamate (CNB) is a new antiseizure medication (ASM) for add-on therapy in adults with refractory epilepsy. The purpose of this study was to investigate the pharmacokinetic variability of CNB and extent of...
OBJECTIVES: Cenobamate (CNB) is a new antiseizure medication (ASM) for add-on therapy in adults with refractory epilepsy. The purpose of this study was to investigate the pharmacokinetic variability of CNB and extent of interactions with other ASMs. METHODS: In this observational therapeutic drug monitoring (TDM) study we included all patients with serum concentrations of CNB and concomitantly used ASMs (2022-2025) from the Section for Clinical Pharmacology, National Center for Epilepsy, Oslo University Hospital. RESULTS: Data from 258 patients included 672 serum CNB concentration measurements (1-7 per patient; 56% women; median age = 36 years, range = 11-77). Mean daily dose and serum concentration at the most recent measurement were 164 mg/day (range = 12.5-400, SD = 88.6) and 53.7 μmol L (range 5-186, SD = 34.8). Intraindividual variation in CNB concentration/dose (C/D) ratios ranged from 6% to 33% (coefficient of variation = 18%); interpatient variability was 34-fold. Comedication was a contributing but variable factor. Mean CNB C/D ratios were affected by strong enzyme inducers (-9%) and inhibitors (+14%) as compared to neutral ASMs (p < .05). Twenty-four concomitant ASMs were used (1-6 per patient, mean = 1.91, SD = .94); clobazam, lamotrigine, and valproate were the most common. After initiating CNB, significant but variable increases in mean C/D ratios of desmethylclobazam (+233%, and +344% for the Cd-clb/Cclb€ ratio, n = 57) and phenobarbital (+36%, n = 15) were observed, as were decreases for lamotrigine (-28%, n = 57) and carbamazepine (-26%, n = 7) (p < .05). For most other ASMs, there were unpredictable changes in individual C/D ratios. SIGNIFICANCE: We demonstrate complex and unpredictable two-way interactions in polytherapy with CNB and pronounced pharmacokinetic variability among patients with refractory epilepsy, elucidating the usefulness of TDM.
Pentanucleotide repeat instability and transmission in benign adult familial myoclonic epilepsy types 1, 4, and 8.
Rakwongkhachon S, Pongpanich M, Srichomthong C … +8 more , Assawapitaksakul A, Tongkobpetch S, Santawong K, Gahl WA, Chunharas C, Landouré G, Yeetong P, Shotelersuk V
Epilepsia · 2026 Mar · PMID 41874439 · Publisher ↗
OBJECTIVE: Benign adult familial myoclonic epilepsy (BAFME) is a rare autosomal dominant disorder characterized by tremor and myoclonic seizures. To date, seven genetic subtypes have been identified, all caused by noncod...
OBJECTIVE: Benign adult familial myoclonic epilepsy (BAFME) is a rare autosomal dominant disorder characterized by tremor and myoclonic seizures. To date, seven genetic subtypes have been identified, all caused by noncoding pentanucleotide repeat expansions-typically TTTTA expansions with additional TTTCA insertions-across distinct loci. Although aberrant repeat expansions are a shared hallmark, it remains unclear whether different BAFME subtypes exhibit similar patterns of repeat length variability and inheritance. We aimed to characterize pentanucleotide repeat structure, repeat length variability across reads, and intergenerational transmission patterns across multiple BAFME subtypes, and to determine whether these mutational dynamics differ among BAFME1, BAFME4, and BAFME8. METHODS: We performed whole-genome long-read sequencing and targeted adaptive sampling long-read sequencing on 18 affected individuals from three multigenerational families with BAFME1 (SAMD12), BAFME4 (YEATS2), and BAFME8 (RAI1). Repeat structure, repeat length variability across reads, and intergenerational transmission dynamics were analyzed. RESULTS: Across patients, 7-33 long reads containing expanded repeats were identified. Several differences in repeat length distributions across reads were observed among the families studied. The BAFME1 family showed comparatively narrower distributions, whereas broader variability was observed in the BAFME4 and BAFME8 families. In BAFME1 and BAFME8, TTTCA repeat length showed a positive correlation with age, consistent with age-associated increases in repeat length variability across reads. Parent-to-offspring transmissions were often associated with increases in repeat length, most prominently in BAFME8. Sibling comparisons further indicated higher variability in TTTCA than in TTTTA repeats. SIGNIFICANCE: Our study demonstrates distinct patterns of repeat length variability and inheritance across the families analyzed. These findings suggest that the genomic context of pentanucleotide expansions may influence repeat behavior and could contribute to phenotypic variability in BAFME.
Clinical characteristics and surgical outcomes of Rasmussen encephalitis: A retrospective dual-center cohort study.
Liu Y, Lv K, Guo H … +13 more , Wu H, Gong P, Chen Z, Deng J, Wang X, Guan Y, Zhou J, Wang R, Liu Q, Cai L, Ji T, Tang C, Luan G
Epilepsia · 2026 Jun · PMID 41874285 · Publisher ↗
OBJECTIVE: Rasmussen encephalitis (RE) is a rare progressive disorder causing drug-resistant epilepsy. Hemispheric surgery is an established treatment, but comprehensive data on postoperative seizure, motor, and cognitiv...
OBJECTIVE: Rasmussen encephalitis (RE) is a rare progressive disorder causing drug-resistant epilepsy. Hemispheric surgery is an established treatment, but comprehensive data on postoperative seizure, motor, and cognitive outcomes are limited. We aimed to evaluate these outcomes and identify associated prognostic factors. METHODS: This dual-center retrospective study included RE patients who underwent hemispheric surgery at two tertiary epilepsy centers in China. Seizure outcomes were classified by Engel class, with Engel class I regarded as seizure-free. Motor outcomes were evaluated using the Motricity Index (MI), Gross Motor Function Classification System (GMFCS), and Manual Ability Classification System (MACS), with stable outcomes defined as improvement or no change between baseline and follow-up. Cognitive function was evaluated using standardized scales. Multivariable Cox regression identified factors associated with seizure and motor outcomes. RESULTS: Eighty-five patients (52 female, 63%) with median follow-up of 2.75 years were included. At last follow-up, 79% were seizure-free after initial hemispheric surgery. Hemispheric disconnection showed better seizure control (92%) than anatomic (67%) or functional hemispherectomy (57%), with shorter surgery and less blood loss. Stable gross motor function was achieved in 94%, whereas 64% experienced worsening fine motor skills. Generalized seizures (hazard ratio [HR] 5.48, 95% confidence interval [CI] 1.63-18.42), contralateral magnetic resonance imaging (MRI) abnormalities (HR 6.43, 95% CI 1.14-36.28), contralateral interictal electroencephalography (EEG) discharges (HR 4.61, 95% CI 1.57-13.51), and type of hemispheric surgery (HR 5.25, 95% CI 1.57-13.51) were associated with seizure persistence. Postoperative seizure-free (HR 4.43, 95% CI 1.61-12.17) and baseline MI (HR .94, 95% CI .91-.96) predicted overall motor stability, whereas fine motor stability was related to epilepsia partialis continua (EPC) duration (HR .50, 95% CI .25-.98), preoperative immunotherapy (HR 3.30, 95% CI 1.13-9.59), and baseline MACS (HR 2.45, 95% CI 1.68-3.57). SIGNIFICANCE: This study suggests that hemispheric surgery is effective in achieving seizure-free and favorable gross motor recovery in RE. Early surgery, attention to contralateral abnormalities, and preoperative immunotherapy may further improve outcomes.
Tissue oxygenation dynamics during transition from seizure to spreading depolarization in rat brain.
Liu J, Gluckman BJ
Epilepsia · 2026 Jun · PMID 41859779 · Full text
OBJECTIVE: Spreading depolarization (SD) is a phenomenon underlying various neurological conditions, including epilepsy. Researchers have suspected that local tissue oxygenation breakdown induces spontaneous SD. In this...
OBJECTIVE: Spreading depolarization (SD) is a phenomenon underlying various neurological conditions, including epilepsy. Researchers have suspected that local tissue oxygenation breakdown induces spontaneous SD. In this study, we investigated the relationship between spontaneous epileptic seizures and SD, with a focus on the role of local tissue oxygenation during the transition from seizure to seizure-associated SD. METHODS: We applied a long pulse voltametric method to characterize local tissue oxygenation and extracellular space (ECS) volume change in the hippocampus (HC) of freely moving epileptic rats (six males and three females). Recordings were performed during the normal state of vigilance, spontaneous seizures, seizure-associated SD events, and their transitions. RESULTS: No significant breakdown in local tissue oxygenation of HC was detected before the SD onset during the seizure to SD transition. In contrast, decreased ECS volume in the HC was observed before SD onset during this transition. SIGNIFICANCE: Using a novel electrochemical approach in freely behaving rats with intact cerebral autoregulation, we demonstrate that there is no significant breakdown of local tissue oxygenation during seizure to SD transition. However, the ECS begins to shrink during seizure, before SD onset, suggesting that ECS shrinkage may play a leading role in this transition. These findings refine our understanding of the mechanisms driving seizure-associated SD and suggest that ECS may represent a potential therapeutic target in epilepsy and SD-associated neurological disorders.
Surgical treatment of epilepsy in polymicrogyria: A subject-level meta-analysis and decision-making framework.
Bosisio L, Viglietti C, Consales A … +6 more , Nobile G, Pacetti M, Tortora D, Mancardi M, Nobili L, Francione S
Epilepsia · 2026 Mar · PMID 41854623 · Publisher ↗
OBJECTIVE: Polymicrogyria (PMG) presents a complex challenge in epilepsy surgery. The optimal surgical strategy and extent of resection, from hemispheric to more limited approaches, remain debated. We aimed to summarize...
OBJECTIVE: Polymicrogyria (PMG) presents a complex challenge in epilepsy surgery. The optimal surgical strategy and extent of resection, from hemispheric to more limited approaches, remain debated. We aimed to summarize subject-level surgical outcomes and identify factors informing procedure selection. METHODS: We conducted a subject-level pooled analysis of 161 patients across 20 retrospective studies, evaluating surgical outcomes (Engel classification), in relation to anatomic extent, surgical procedure, use of intracranial electroencephalography (ICEEG), and other decision-influencing factors. RESULTS: At ≥12 months follow-up, ~70% of patients achieved seizure freedom (Engel Class I). In our univariate analysis Engel Class I outcomes were associated with shorter epilepsy duration (8.05 vs 11.92 years, p = 0.009). Hemispheric PMG was linked to earlier seizure onset (p = 0.02) and a higher incidence of epileptic encephalopathy with spike-wave activation in sleep (p < 0.0005). Among unilateral non-hemispheric and bilateral PMG cases, seizure-freedom rates were similar between hemispheric and more limited resections, but the latter were associated with a lower incidence of new or worsened motor deficits. Mixed-effects logistic regression (n = 160) showed that hemispheric surgery increased the odds of seizure freedom but without statistical significance (odds ratio [OR] = 3.52, p = 0.055). ICEEG did not significantly influence seizure outcomes but may play a key role in identifying eloquent cortex and guiding safer, tailored resections. SIGNIFICANCE: In PMG-related epilepsy, surgical strategy must balance seizure control with preservation of function. ICEEG (especially stereo-EEG [SEEG]) remains a valuable tool for functional mapping and tailored resections.
Women with epilepsy: Evidence-based counseling across the lifespan.
Tettenborn B, Ramantani G, Flügel D … +5 more , Gaus V, Schubert-Bast S, Sellitto E, Bausch J, Schmitz B
Epilepsia · 2026 Jun · PMID 41854534 · Full text
Women with epilepsy (WWE) encounter distinct and evolving challenges across the lifespan that require clinical management extending beyond seizure control alone. Although awareness of sex-specific aspects of epilepsy has...
Women with epilepsy (WWE) encounter distinct and evolving challenges across the lifespan that require clinical management extending beyond seizure control alone. Although awareness of sex-specific aspects of epilepsy has increased, important gaps remain in their integration into routine care. This review synthesizes current evidence on epilepsy management across key life stages, including adolescence and transition to adult care, reproductive health, contraception, fertility and pregnancy, lactation, menopause, and bone health. It integrates recent literature with expert interpretation in alignment with contemporary clinical guidelines, with the aim of enhancing clinical applicability. Hormonal changes, bidirectional interactions between antiseizure medications (ASMs), and reproductive physiology as well as shifting psychosocial demands influence seizure patterns, treatment efficacy, and long-term health outcomes in WWE. Particular focus is placed on interactions between epilepsy, endocrine regulation, and ASM therapy, and on teratogenic and neurodevelopmental risks associated with specific ASMs. Effective care for WWE requires continuous, individualized counseling that adapts to changing priorities and risks over time. Structured transition processes, evidence-based counseling on contraception and pregnancy, therapeutic drug monitoring during pregnancy, and transparent communication regarding fetal risks of ASMs are essential components of high-quality care. Beyond the reproductive years, seizure changes during menopause and the cumulative impact of long-term ASM exposure, particularly on bone health, require surveillance and prevention. Despite advances in pregnancy registries and treatment recommendations, participation in registries is low, and evidence outside pregnancy remains limited. Awareness of sex-specific epilepsy issues continues to be insufficient among both WWE and health care professionals. Addressing these gaps will require improved education, coordinated multidisciplinary care, and expanded research efforts to support patient-centered, lifelong care for WWE.
Agreement and 2-year trajectories of youth- and parent-reported health-related quality of life in youth with epilepsy treated with surgery vs medical therapy.
Smith ML, Puka K, Widjaja E
Epilepsia · 2026 Jun · PMID 41854511 · Full text
OBJECTIVE: This cohort study examined the agreement between youth- and parent-reported health-related quality of life (HRQOL) of children treated with epilepsy surgery compared to medical therapy. A second aim was to eva...
OBJECTIVE: This cohort study examined the agreement between youth- and parent-reported health-related quality of life (HRQOL) of children treated with epilepsy surgery compared to medical therapy. A second aim was to evaluate whether changes in HRQOL over 2 years differed between the two groups, and to determine whether these trajectories differed by informant (youth or parent). METHODS: A total of 255 youth-parent dyads participated, of whom 95 youth underwent epilepsy surgery and 160 continued medical management. Participants completed the KIDSCREEN-27 at baseline, 6-month, 1-year, and 2-year follow-up. Youth-parent agreement was evaluated at the individual level as well as at the group level. Linear mixed models were used to evaluate changes in HRQOL over time. RESULTS: Among 255 youth, 46% were female, and ages ranged from 8 to 18 years (mean 13 years) at baseline. Most parents were female (85%) and 40-49 years of age (58%). The surgical and medical group were largely similar across baseline characteristics. Agreement across HRQOL domains ranged from fair to good intraclass correlation coefficient (ICC .32-.66). Although average youth-parent differences were small (-1 to +3 points), Bland-Altman plots showed large discrepancies, and substantial differences between dyads were frequent. Youth reported increasing Physical Well-being and School Environment scores in the first year after surgery and remaining stable or slightly decreasing thereafter. In contrast, parent-reported trajectories for Physical Well-being and School Environment did not show a significant difference. For other domains-Psychological Well-being, Autonomy and Parent Relation, and Social Support and Peers-no differences were identified across treatment groups, and findings were consistent among youth and parent reports. SIGNIFICANCE: The results emphasize the need for considering the perspective of youth as well as their parents when evaluating the outcomes of surgery or other treatments for epilepsy.
Correction to "Long-term neuroplasticity in language networks after anterior temporal lobe resection".
Epilepsia · 2026 May · PMID 41848829 · Publisher ↗
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Response: An etiology-driven framework for status epilepticus and ictal-interictal continuum.
Bosque-Varela P, Trinka E, Kuchukhidze G
Epilepsia · 2026 May · PMID 41848636 · Full text
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An etiology-driven framework for status epilepticus and ictal-interictal continuum.
Lattanzi S
Epilepsia · 2026 May · PMID 41848611 · Full text
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