Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy (DEE) characterized by multiple seizure types and high resistance to antiseizure medication (ASM), often necessitating nonpharmacologic therapies, including neuromodulation. Responsive neurostimulation (RNS), a closed-loop brain-responsive neuromodulation device, has emerged as an adjunctive treatment option for drug-resistant epilepsy (DRE), but evidence on its safety and effectiveness in LGS remains limited. This study examines real-world outcomes of RNS therapy in patients with LGS-associated DRE. This retrospective multicenter study included patients with LGS who underwent RNS implantation before December 2024 across four Level 4 National Association of Epilepsy Centers (NAEC) in the United States. Demographic, clinical, surgical, and outcome data were systematically collected using a standardized case report form and analyzed. Thirty-seven patients met inclusion criteria. At the time of RNS implantation, 95% of patients were pediatric (mean age 12.9 years, range 3.6-28.8) with a median follow-up of 24.5 months. All patients had generalized tonic seizures; additional seizure types included tonic-clonic (62%), atonic (50%), atypical absence (19%), and other (54%). The pooled responder rate (≥50% seizure reduction) was 62%, including 10% with ≥90% reduction. Thalamic-only stimulation of the bilateral centromedian nucleus (CMN) was the most common electrode configuration (76%), followed by cortico-thalamic targeting to the CMN and bi-frontal regions (18%). Among responders, 83% received thalamic-only CMN stimulation. ASM reduction occurred in 10% of patients. Adverse events were reported in 13%, primarily implant-related infections, with 4 patients requiring explantation. Stimulation-related side effects occurred in 27% and resolved with programming adjustments in 80%. RNS targeting thalamic and cortico-thalamic networks resulted in seizure reduction in the majority of this predominantly pediatric LGS cohort. Therapy was generally well-tolerated with few serious adverse events, supporting its potential role as an adjunctive treatment option for DRE in LGS. Lennox-Gastaut syndrome is a severe form of epilepsy that is often hard to control with medications. This study evaluated responsive neurostimulation (RNS), an implanted device that monitors brain activity and delivers electrical stimulation to help stop seizures before they spread. In 37 mostly pediatric patients, about 60% had their seizures reduced by at least half, and some improved even more. The treatment was generally safe, and most side effects could be managed by adjusting the device.

Atypical absence status epilepticus (AASE) is a rare subtype of nonconvulsive status epilepticus (NCSE), characterized by clouding of consciousness and continuous or fluctuating epileptiform activity, generally at a frequency below 3 Hz. Only sparse literature exists on the genetic conditions associated with it. We performed a systematic review to identify the genetic diagnoses in which AASE has been described, and examined the available clinical, EEG, treatment and outcome details. The protocol was registered in PROSPERO and reporting followed PRISMA guidelines. We searched public databases for combinations of the terms: "atypical absence status epilepticus," "status epilepticus," "non convulsive status epilepticus," and "gene," "genetics," "epileptic encephalopathy," "developmental and epileptic encephalopathy," "DEE." Only original articles in English were included. We identified 34 publications reporting 97 patients with AASE and an underlying genetic condition. Most patients had a chromosomal abnormality (88%), in particular ring chromosome 20 (53% of the total patients) and Angelman syndrome caused by a 15q11-q13 deletion (31%). Seven epilepsy genes (UBE3A, CNKSR2, TRPM3, KCNH2, NEXMIF, SYNGAP1, GABRB1) were found in which a clinical and electrographic picture consistent with AASE was described. Therefore, in the context of a possible genetic diagnosis, AASE has been reported mainly in chromosomal disorders. However, this condition is likely underrecognized and underreported, particularly in monogenic epilepsies. Therefore, a deeper phenotyping and a more standardized use of classification terms would be necessary both for clinical and research purposes. PLAIN LANGUAGE SUMMARY: We reviewed the scientific literature to find out in which genetic conditions a rare EEG and clinical pattern, called atypical absence status epilepticus, has been described. We found that this pattern is mainly reported in patients with changes in chromosome structure, such as ring chromosome 20 and Angelman syndrome. Among single-gene (monogenic) forms of epilepsy, it has been described in association with seven genes (UBE3A, CNKSR2, TRPM3, KCNH2, NEXMIF, SYNGAP1, GABRB1). When clinicians suspect a genetic cause of epilepsy and this finding is present, they should consider checking also for chromosomal changes.

Human telomerase reverse transcriptase (hTERT) is a key determinant of telomere maintenance and cellular aging. Oxidative stress plays a role in neurodegenerative processes by causing cellular damage through increased reactive oxygen species. Our study aimed to reveal the relationship between hTERT and oxidative stress in the pathophysiology of epilepsy. The study included 45 individuals diagnosed with epilepsy and 55 healthy controls. hTERT concentration, total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), and thiol-disulfide homeostasis were measured in serum samples. A significant decrease in hTERT levels, an increase in oxidative stress markers (TOS, OSI), and a decrease in antioxidant levels (TAS, SOD), and total and native thiol levels were determined in epilepsy patients. In addition, a significant and negative correlation was found between hTERT and native thiol. Our study suggested that the interaction between oxidative stress and hTERT levels in the pathophysiology of epilepsy may play an important role in seizure generation and progressive neural damage. This study will form the basis for further research and guide the identification of potential biomarkers for treating epilepsy. We measured the levels of a protective protein that helps preserve chromosomes and several markers of cell stress in people with epilepsy and healthy volunteers. People with epilepsy showed lower levels of this protective protein, weaker antioxidant defenses, and higher oxidative stress. We also found that lower protein levels were linked to fewer molecules that guard cells from damage. These changes may help explain why seizures occur and why the brain can suffer ongoing injury in epilepsy.

ObjectiveSialidosis type I (ST‐1) is an autosomal‐recessive, very rare, progressive lysosomal storage disorder caused by pathogenic variants in NEU1. It is clinically characterized by progressive ataxia, myoclonic seizures (MS), bilateral tonic–clonic seizures (BTCS), and distinctive ophthalmological findings. Given the lack of curative options, in this study, we investigated symptomatic treatment strategies, with a particular focus on the efficacy of antiseizure medications (ASMs).MethodsWe describe the clinical course of a patient followed from diagnosis to 18 years of age, and review seven additional cases from our cohort. In parallel, we conducted a narrative review of the literature (PubMed, January 2010–September 2025) to identify published reports containing therapeutic data.ResultsTherapeutic responses were evaluated in a total of 33 cases (8 from our cohort, 25 from published sources). Although available data are insufficient to define standardized treatment guidelines, some ASMs, such as ACZ, PER, LEV, VPA, CZP, and ZNS, demonstrated fairly consistent efficacy in managing MS and BTCS. Sodium oxybate or deep‐brain stimulation may be considered in refractory cases.SignificanceProspective documentation of clinical course and treatment outcomes—ideally through an international registry—is crucial to improve patient care and inform therapeutic strategies.Plain Language SummarySialidosis type I (ST‐1) is a very rare genetic disorder causing movement problems and seizures, with no cure available yet. We followed 8 patients and reviewed 25 published cases to assess treatments focusing on myoclonic seizure (MS) control. Some antiseizure medications showed benefit. However, we have too little data to make clear recommendations. To improve patients' treatment and to choose the most appropriate therapy, it would be important to follow patients over a longer period of time, for example, in an international registry.

ObjectiveFocal cortical dysplasia (FCD) is a leading cause of drug‐resistant epilepsy and is associated with sleep‐related seizures, yet the underlying electrophysiological mechanisms during different brain states remain poorly understood. We investigated whether fast oscillations (FOs) within the seizure onset zone (SOZ) and irritative zone (IZ) change significantly during sleep compared with wake in FCD patients. We analyzed multiple frequency bands—beta (14–20 Hz), gamma (40–80 Hz), ripple (80–250 Hz), and broadband BGR (14–250 Hz) to provide comprehensive information about sleep‐related changes. We hypothesized that sleep‐related FO changes would be associated with sleep‐related epilepsy, frontal location, or FCD type II.MethodsWe examined intracranial EEG (iEEG) recordings from 22 FCD patients undergoing presurgical evaluation between 2010 and 2023, with a mean age of 25.3 ± 12.8 years and a disease duration of 17.7 ± 12.3 years. Using semiautomated detection, we compared FO rates between wake and sleep epochs, focusing on contacts within IZ and SOZ. Distance‐based multivariate analysis of variance (MANOVA) was employed for patient‐level analysis, accounting for spatial organization and enabling multiband evaluation.ResultsAnalysis of 67 ± 28 bipolar iEEG contact pairs per patient revealed distinct sleep‐related patterns. In SOZ, gamma oscillations showed significant increases in 10/22 patients (45%), followed by BGR in 7/22 patients (32%). IZ exhibited stronger changes, with BGR and gamma showing significance in 13/22 patients each (59%) with high concordance. Gamma oscillation rates in SOZ increased in patients with confirmed sleep‐related epilepsy (p < 0.05), while no associations were found with frontal location or FCD type II.SignificanceGamma oscillations showed robust sleep‐related increases in SOZ, while gamma and BGR frequencies demonstrated strong changes in IZ, often occurring simultaneously. These findings suggest gamma oscillations, complemented by BGR analysis, may qualify as markers for characterizing sleep‐related changes in FCD patients, potentially advancing understanding of mechanisms underlying sleep‐related seizures.Plain Language SummaryFocal cortical dysplasia (FCD) is a brain malformation that causes difficult‐to‐treat epilepsy, with patients experiencing seizures mainly during sleep. We studied electrical brain waves in 22 FCD patients using electrodes placed directly within or on the brain during pre‐surgery evaluation. We compared brain wave activity between wake and sleep, focusing on fast brain waves. We found that fast brain waves, especially gamma waves, increased significantly during sleep in brain areas where seizures start, particularly in patients whose seizures occur mainly during sleep. These findings potentially help us better understand why seizures happen more often during sleep in FCD patients.

ObjectiveThe long‐term effects of epilepsy surgery (ES) or vagus nerve stimulation (VNS) on antiseizure medication (ASM) usage and status epilepticus (SE) diagnosis in real‐world pediatric drug‐resistant epilepsy (DRE) populations remain unclear. This study aimed to provide a more comprehensive understanding of how VNS and ES affect ASM usage and SE manifestations in pediatric DRE.MethodsWe conducted a nationwide, retrospective cohort study using the Korean Health Insurance Review and Assessment Service database from January 1, 2007, to December 31, 2022. Pediatric patients (<18 years) diagnosed with DRE were categorized into ASM‐only, VNS, and ES groups. Changes in ASM usage and SE diagnostic rates were assessed.ResultsA total of 6075 pediatric patients with DRE were included (ASM‐only, n = 5407; VNS, n = 217; ES, n = 451). Although the VNS and ES groups had more severe epilepsy at baseline, both interventions significantly reduced ASM usage, albeit with distinct trajectories. ES led to a sharp reduction in ASM usage immediately postoperatively, followed by stabilization, with approximately one‐third of the patients discontinuing ASM by the end of follow‐up. VNS stabilized ASM usage rather than reducing it, with fewer than 10% of patients discontinuing ASM. Both interventions were associated with significant decreases in SE diagnostic rates after the intervention (p = 0.007 and 0.02, respectively), but no statistically significant difference was found in the overall SE rates among the three groups (p = 0.18).SignificanceThese findings demonstrate that VNS and CES positively impact ASM usage, reduce the incidence of SE, and underscore the need for timely intervention to optimize outcomes.Plain Language SummaryWe studied children with drug‐resistant epilepsy who were treated with either vagus nerve stimulation (VNS) or brain surgery for epilepsy. We found that brain surgery often led to a large and lasting reduction in seizure medication, whereas VNS helped stabilize medication use. Both treatments were linked to fewer cases of status epilepticus, a severe type of seizure emergency. These findings suggest that VNS and surgery may help reduce medication burden and protect against serious seizures in children with hard‐to‐treat epilepsy.

ObjectiveDrug‐resistant epilepsy (DRE) is defined as the failure of two antiseizure medications (ASMs) to achieve complete seizure control, affecting approximately 30% of epilepsy patients. In some cases, additional ASMs and surgical approaches are also unsuccessful. Ultra‐Refractory Epilepsy (URE) is a newly described entity, characterized by the failure of six distinct epilepsy treatment strategies, including ASMs, surgical resection, and neurostimulation techniques. This study aimed to analyze demographic and clinical data of URE patients managed at the Brno Epilepsy Center, a member of the European Reference Network (ERN)—EpiCARE.MethodsWe conducted a retrospective cohort study with a prospective follow‐up component. Adult patients hospitalized for epilepsy at the Brno Epilepsy Center between 2017 and 2023 were retrospectively identified, and their outcomes were prospectively assessed in February 2025 through medical record review and structured telephone interviews. URE patients were identified, and their demographic and clinical data were analyzed.ResultsIn this study, 1034 patients' charts were reviewed, and 62 patients (6%) met the criteria for URE. In the URE cohort, the median age of epilepsy onset was 9 years (range 1–60 years), and the median age at the time of evaluation was 35 years (range 21–67 years). The median seizure frequency was nine seizures per month (range 1–900), with 26 (42%) of patients experiencing extremely high seizure frequencies (>20 seizures/month). Structural etiology was the most common cause (29 [47%] patients). Among the cohort, 57 (92%) patients received a combination of ASMs, surgical resection, or neurostimulation, while only 5 (8%) patients were managed exclusively with ASMs.SignificanceURE represents an extreme therapeutic challenge within epilepsy centers. The high seizure burden and limited treatment response in this population highlight the urgent need for novel therapeutic strategies and further research into this newly defined entity.Plain Language SummaryUltra‐refractory epilepsy (URE) is a newly described form of extremely difficult‐to‐treat epilepsy. In our study of 62 patients, all had already failed at least six different treatment attempts, including medications, brain surgery, or nerve stimulation. Most patients continued to have frequent seizures despite all available therapies, and only a small minority achieved long‐term seizure freedom. These findings show that URE is a severe condition with a major unmet medical need, highlighting the importance of developing new treatment strategies.