Epilepsia最新文献

There is debate on the predictive value of multiday seizure cycles versus simple statistical baselines. Multidien seizure cyclicity is a prevalent, patient-specific phenomenon with promise for epilepsy management. We challenge the assertion that cycle tracking is no better than a moving average, which is an inherently retrospective model that lags changes in seizure likelihood. This commentary compared a causal cyclic forecast to a prospectively applied moving average across a large seizure diary cohort (n = 768) and two gold-standard chronic EEG cohorts (n = 24). For the EEG and diary cohorts, cycle tracking demonstrated significantly superior accuracy to the moving average for both hourly and daily forecasts (p < 0.0001), using multiple performance metrics. These results confirm that event-based cyclical models offer more accurate, simulated real-world forecasts. Robust forecasting tools must prioritize the detection and modeling of seizure cycles to move beyond simple baseline performance and provide actionable clinical utility.

Objective: To estimate the incidence and determine the consequences of status epilepticus (SE) associated with idiopathic generalized epilepsy (IGE) in adults.

Methods: Based on International Classification of Diseases, Tenth Revision (ICD-10) codes we extracted patients with IGE in the period from January 1, 2005 to December 31, 2018, and divided them into two groups: patients with and without a hospitalization with SE before the end of the study. Each patient was matched with 10 normal population controls from the Danish National Patient Register based on age, sex, and geography. Survival, drug resistance, medical history, and surrogate markers for social status were compared.

Results: We identified 6295 IGE patients and 62 950 normal population controls with slight female preponderance (3338 female; 55.5%). At least one admission with SE was documented for 4.5% (n = 283 patients), of which 57.2% (n = 162) had two or more admissions with SE. The comparison of patients with and without SE before first-time admission for SE showed higher age, surrogate markers for lower social status (affiliation with the labour market, household income, marital status), indicators of more severe IGE (number of antiseizure medications tried, prescription patterns suggestive for drug resistance), and higher psychiatric comorbidity in patients with SE than without. It is important to note that an episode of SE only transiently and slightly affected markers for social status. All-cause mortality was increased in IGE patients with SE (17.7%) as compared to 6.2% in age-matched population controls.

Significance: SE in IGE has a high rate of occurrence and is associated with drug-resistant IGE, poor social status, and psychiatric comorbidity already before the first episode of SE. Although the social impact of SE in the short term remains limited, all-cause mortality after SE is increased.

Objective: This study aimed to identify risk factors and develop a predictive scoring system for autoimmune-associated epilepsy in subjects with autoimmune encephalitis presenting with new onset refractory status epilepticus (NORSE).

Methods: This retrospective, multicenter, cohort study included subjects who presented with NORSE at the onset of autoimmune encephalitis and had at least 24 months of follow-up after immunotherapy. The outcome was the development of autoimmune-associated epilepsy, defined as persistent seizures despite adequate immunotherapy and absence of active inflammation. Factors independently associated with the outcome were identified through a backward stepwise selection. Adjusted regression coefficients of each independent predictor were transformed to produce a points-based risk-scoring system.

Results: Seventy participants were included (median age = 24.2 years, 38.6% male). During a median follow-up of 53 months, 54.3% of subjects developed autoimmune-associated epilepsy. Status epilepticus duration ≥ 10 days (odds ratio [OR] = 31.14, 95% confidence interval [CI] = 2.12-456.87, p = .012), positivity for antibodies against surface antigens (OR = .12, 95% CI = .02-.85, p = .034), bitemporal magnetic resonance imaging (MRI) abnormalities suggestive of autoimmune encephalitis during acute stage (OR = 49.80, 95% CI = 2.95-841.77, p = .007), and interictal epileptiform discharges during electroencephalographic (EEG) follow-up (OR = 71.32, 95% CI = 6.48-785.32, p < .001) were independently associated with the study outcome. The duration-antibodies-MRI-EEG (DAME) score was developed as an integer-based scoring system predictive of autoimmune-associated epilepsy. With an optimal cutoff of ≥3 points, it yielded a sensitivity of 86.8%, a specificity of 87.5%, and an overall accuracy of 87.1%.

Significance: The DAME score could serve as a user-friendly score to predict the risk of autoimmune-associated epilepsy in patients with NORSE due to autoimmune encephalitis.

Objective: To examine the performance of single-item global ratings (SIGRs) and multi-item scales (MISs) in epilepsy research, and assess the influence of diverse constructs, study designs, and statistical methods.

Methods: Systematic scoping review following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Joanna Briggs Institute guidelines. MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Register of Controlled Trials were searched from 1980 onward. English-language articles including ≥30 persons with epilepsy and using at least one SIGR and one MIS were analyzed. Citation screening at all levels was done independently by two reviewers; data extraction was standardized. We analyzed individual measurements of effect magnitude for SIGRs and MISs. For meta-analyses, correlation-related metrics were transformed to Pearson r and Fisher z transformed, and effect-size metrics were converted to Cohen's d with Hedges g correction. Multilevel meta-analyses were used to account for data heterogeneity and clustering of effect sizes within studies, and to assess the influence of predefined moderators. Publication bias was assessed with standard methods.

Results: A total of 18 267 citations were identified, and 58 studies were included. Effect magnitude was medium to large across measurements, and it was slightly larger for MISs than for SIGRs, both for correlations and effect sizes (difference = .04, p < .001). Overall, SIGRs and MISs were comparable, and statistically significant differences did not cross effect thresholds (from small to medium or medium to large). Correlations and effect sizes for SIGRs and MISs were lowest in studies involving children and when assessing change; and for SIGRs when Global Clinical Impression (GCI) formats were used.

Significance: SIGRs are likely comparable to MISs across multiple study and statistical contexts. However, in certain clinical scenarios, MISs will outperform SIGRs and vice versa. Researchers should carefully consider whether SIGRs, MISs, or a combination is most appropriate to answer the research question.

Objective: This study aims to evaluate the effect of maternal antiseizure medication (ASM) exposure on fetal malformations, accounting for specific periods of medication use during pregnancy and differentiating between monotherapy and dual therapy.

Methods: Using data from the Korean National Health Insurance Service between 2010 and 2020, we conducted a population-based retrospective cohort study of pregnant women with epilepsy who were administered ASMs during pregnancy and those who were not, to assess the associated risk of congenital malformations. Participants were divided into four subgroups based on ASM exposure: Subgroup 1, first trimester (T1) exposure (first 12 weeks); Subgroup 2, exposure limited to the first 140 days; Subgroup 3, exposure only after day 141; Subgroup 4, continuous exposure. Each subgroup was analyzed separately to compare the effects of monotherapy and dual therapy. The primary outcome was the relative risk (RR) of congenital malformations associated with ASM monotherapy and dual therapy.

Results: Between 2012 and 2020, 1 916 583 women gave birth. Among these, 8939 (.47%) were diagnosed with epilepsy and required continuous ASM therapy for part or all of the observation period, whereas 4968 women with epilepsy had no ASM exposure during pregnancy and served as the unexposed comparator group. Subgroup 2 showed lower adjusted RR of congenital malformations with monotherapy and dual therapy. In dual therapy, lamotrigine was linked to an increased risk of overall malformations in Subgroups 1 (adjusted RR = 1.81, 95% confidence interval [CI] = 1.22-2.70, p = .0033) and 4 (adjusted RR = 1.81, 95% CI = 1.21-2.70, p = .0039). Valproate dual therapy in Subgroup 4 showed higher risk of overall malformations (adjusted RR = 3.40, 95% CI = 1.36-8.48, p = .0086) and cardiac malformations (adjusted RR = 5.50, 95% CI = 1.29-23.51, p = .0214).

Significance: Prolonged ASM exposure throughout pregnancy was associated with a significantly increased risk of malformations compared with exposure limited to T1 or to the first half of pregnancy.

The artificial intelligence (AI) revolution is upon us. It will inevitably form a central component of epilepsy workflows and patient advocacy. Therefore, it behooves us as health care providers to ride the crest of this wave and guide its direction for the benefit of all people with epilepsy. Emerging AI-based solutions include decision support tools, automated interpretation of electroencephalography (EEG) and brain imaging, and wearable devices that detect seizures and improve patient safety. Pipelines, including decentralized approaches and federated learning, are now being built that will democratize access and facilitate the next generation of AI tools for the global epilepsy community. Despite this, enduring issues remain incompletely addressed. For example, AI requires high volumes of data, leading to concerns about ethical ownership, stewardship, and privacy. Few AI-based tools have progressed from derivation to validation stages, and only rare exceptions undergo real-world evaluation. Inadvertent harmful algorithmic and decision allocation biases also continue to represent major risks to the global epilepsy population. Additional barriers include geographical disparities in computing resources, proprietary ownership of electronic health records, EEG, and brain-imaging platforms, and greenhouse gas emissions related to the demanding power requirements of AI. Therefore, to fully avail ourselves of the benefits of AI, we assert that ethical, equitable, and effective AI for epilepsy requires collaboration from the entirety of the global epilepsy community. Fundamental to this is early and deliberate engagement of people from low- and middle-income countries to ensure that AI-based solutions do not exacerbate existing global disparities. Ultimately, we advocate for "decision intelligence" approaches to the development of AI-based epilepsy solutions, which involves early engagement of all interest-holders to ensure that the correct questions are addressed and the right technical approaches are deployed to maximize value for the global epilepsy community.

Objective: This study was undertaken to describe weaning practices following ketogenic diet therapy (KDT) in children with epilepsy and to identify clinical factors associated with seizure exacerbation or antiseizure medication adjustments during or after weaning from KDT.

Methods: This retrospective observational study examined patients who initiated and discontinued KDT between 2016 and 2022 at a tertiary epilepsy center. Patients with GLUT1 deficiency, ongoing KDT, or less than 1 year of follow-up postdiscontinuation were excluded. Clinical, electroencephalographic (EEG), magnetic resonance imaging, KDT response, weaning duration, and seizure outcomes were analyzed. Responders were defined by ≥50% seizure reduction. Seizure worsening and/or antiseizure medication (ASM) adjustments during weaning were the primary outcomes.

Results: Among 57 evaluable patients, 49% were responders and 25% became seizure-free. During weaning, 62% experienced seizure exacerbation or required ASM modifications. Unfavorable outcomes were significantly associated with shorter KDT duration, shorter weaning periods, higher ASM burden, and abnormal preweaning EEG. Among responders, seizure worsening was not significantly linked to weaning speed alone. At 1 year, seizure freedom was more common in patients who did not experience any issue during the weaning (65% vs. 30%, p = .009).

Significance: Our findings underscore the importance of individualized KDT discontinuation plans based on efficacy, EEG activity, and ASM burden. Although prolonged weaning was more common in responders, weaning duration alone did not predict outcomes. These results highlight the need for prospective studies to define optimal weaning strategies for KDT.

Objective: Addressing the poorly understood impact of pediatric epilepsy on neurodevelopment, this large-scale study delineates age- and sex-stratified neurostructural trajectories in magnetic resonance imaging (MRI)-negative pediatric epilepsy to identify periods of maximal developmental divergence from healthy controls.

Methods: In this multicenter, cross-sectional study, we analyzed T1-weighted MRI from 957 patients with MRI-negative epilepsy and 962 controls (aged 4-12 years). Generalized additive models for location, scale, and shape modeled sex-stratified developmental trajectories of global brain metrics. Voxel- and surface-based morphometry compared cortical morphology and regional gray matter volume (GMV) between groups across yearly age bins (familywise error-corrected p < .05).

Results: Compared to controls, patients showed reduced total intracranial volume, GMV, cerebrospinal fluid volume, and cortical thickness and significantly increased white matter hyperintensity burden. Key findings on developmental trajectories include an atypical trajectory of total surface area, a premature cortical thickness peak at approximately age 7 years, and a white matter hyperintensity (WMH) burden peak at approximately age 8 years. From ages 4 to 9 years, patients displayed widespread cortical morphological delays, most prominently affecting limbic and sensorimotor networks, which appeared to normalize after age 10 years. Unlike the GMV atrophy seen in adults, pediatric patients showed limbic expansion (5-6 years), thalamic hypertrophy (9-12 years), and cerebellar volumetric shifts.

Significance: Our findings indicate that pediatric epilepsy is a disorder of aberrant neurodevelopment with two distinct signatures. First, we identify a critical 4-9-year vulnerability window characterized by profound but transient deviations, including atypical cortical maturation, increased WMH burden, and widespread morphological delays. These delays appeared to normalize after age 10 years, a finding that requires longitudinal validation. Second, we uncover a progressive, potentially persistent alteration: a hierarchical expansion of gray matter initiating in the limbic system and later involving the thalamus. These signatures provide distinct biomarkers to differentiate transient disruption from ongoing network reorganization, offering new targets for timed interventions.

Objective: One-third of patients with epilepsy, particularly those with mesial temporal lobe epilepsy (MTLE), remain resistant to medication. Resective surgery, the gold standard, is highly invasive and carries significant risks. Here, using a mouse model, we explored the potential of microbeam radiation therapy (MRT), a new technique based on the spatial microfractionation of high-flux X-rays, as a non-invasive alternative for treating MTLE.

Methods: MTLE was modeled in male C57BL6/J mice via unilateral kainate injection in the dorsal hippocampus. Mice with magnetic resonance imaging (MRI)-validated hippocampal sclerosis (HS) were irradiated at the European Synchrotron Radiation Facility (ESRF) using MRT with either a single trajectory (peak doses = 125-500 Gy) or multiple trajectories (2 or 5 ports at a cumulated peak dose of 125 Gy at the target). Their focal seizures were then monitored with use of electroencephalography (EEG) during 8 weeks, upon which immunochemistry was performed to assess potential tissular toxicity.

Results: Anteroposterior 1-port MRT significantly reduced EEG-recorded focal seizures at 125 and 250 Gy, in a dose-dependent manner. However, increased mortality was observed at 500 Gy. Immunohistolabeling revealed neuronal loss (revealed by NeuN staining), microgliosis (revealed by Iba1 straining), and astrogliosis (revealed by GFAP staining) limited to the microbeam tracks at all doses in the injected hippocampus and adjacent brain structures (e.g., cortex). Five-port MRT with a peak dose of 125 Gy at the target improved the antiepileptic effect, whereas no significant tissue alterations outside the microbeam tracks were detected by histological assessment.

Significance: This proof-of-concept study highlights MRT as a promising non-invasive therapy for drug-resistant focal epilepsies with optimal peak doses of 125-250 Gy, and it suggests that distributing the dose through multiple angles optimizes the therapeutic effect. MRT could provide a safer alternative to surgery, warranting further investigations.