Epilepsia Open最新文献

Polymicrogyria (PMG) is a rare malformation of cortical development (MCD) characterized by abnormal neuronal architecture, often associated with epilepsy. Neurosurgical interventions have been explored, but their effectiveness remains a subject of ongoing research and debate. This systematic literature review aims to provide a comprehensive analysis of surgical interventions for epilepsy in PMG individuals, their outcomes, complications, and factors influencing surgical decision-making. This systematic review, conducted according to PRISMA guidelines and registered on PROSPERO (CRD420251010221), analyzed studies on individuals with PMG and epilepsy undergoing neurosurgical treatment. A structured search across five databases was performed. Two reviewers independently selected and extracted data on clinical characteristics, surgical techniques, and outcomes, with seizure control assessed through Engel and ILAE classifications. Statistical analyses included Chi-square and Mann-Whitney U tests. Study quality was evaluated. A total of 47 studies involving 225 patients were included, mostly consisting of case reports or series. The majority of patients underwent resective surgery or hemispherotomy. Postsurgical outcomes were evaluated using Engel or ILAE classifications in 178 cases: 64.61% achieved seizure freedom (Engel/ILAE I). A shorter epilepsy duration was significantly associated with better outcomes. Only a minority received neuropsychological assessments, with cognitive improvements observed mainly in patients operated at a younger age. Postoperative complications were discussed. This review highlights the potential effectiveness of neurosurgical interventions in selected patients with PMG and drug-resistant epilepsy. Despite the overall encouraging seizure outcomes, the limited and heterogeneous reporting of cognitive and quality-of-life measures underscores the need for more comprehensive and standardized pre- and postsurgical assessments to better inform clinical decision-making and long-term management. PLAIN LANGUAGE SUMMARY: This study looked at the effects of brain surgery in people with epilepsy caused by polymicrogyria, a condition where the brain does not form properly before birth and develops an unusual surface. Many patients became seizure-free or had fewer seizures after surgery, especially when performed at an earlier stage. More research is needed to understand how surgery affects mental functions (e.g., memory, attention) and quality of life of these patients.

The FBXW7 gene encodes a substrate-recognition component of the Skp1-Cul1-F-box (SCF) E3 ubiquitin ligase complex, which targets key regulatory proteins for proteasomal degradation. Recently, loss-of-function FBXW7 variants have been associated with a novel neurodevelopmental disorder characterized by heterogeneous clinical features. Most reported pathogenic variants cluster within the WD40 domains, while variants in other regions, such as the F-box domain, remain poorly characterized. In this study, we performed trio-exome sequencing on a 3-year-old girl with Early-Onset Childhood Absence Epilepsy. We analyzed the identified FBXW7 variant using multiple in silico tools for pathogenicity prediction and structural modeling. Clinical phenotype was compared with previously reported cases. We identified a novel de novo missense variant in FBXW7, c.926G>C; p.(Arg309Pro), affecting a highly conserved residue in the F-box domain. Notably, unlike prior cases predominantly associated with WD40 domain variants and severe phenotypes, our patient exhibited a much milder clinical presentation consisting of isolated, drug-responsive absence seizures without intellectual disability. Structural modeling predicted significant impairment in protein-protein binding affinity, particularly with the SCF complex component SKP1, supporting a potentially disruptive effect of the p.(Arg309Pro) substitution on complex assembly. Overall, our findings expand the genotypic and phenotypic spectrum of FBXW7-related disorders. Variants in the F-box domain may result in milder neurological phenotypes compared to those in the WD40 domains, suggesting domain-specific effects and potentially distinct pathogenic mechanisms. PLAIN LANGUAGE SUMMARY: The FBXW7 gene helps regulate the stability of many proteins essential for brain development and function. Changes in this gene have recently been linked to neurodevelopmental disorders with epilepsy. We identified a new FBXW7 variant in a 3-year-old girl with early-onset absence epilepsy. Computer-based modeling suggests that this change weakens the protein's normal interactions. Our findings broaden the spectrum of FBXW7-related disorders and indicate that variants in different gene regions may result in variable clinical severity.

Objective: CDKL5 deficiency disorder (CDD) is an early-onset developmental and epileptic encephalopathy characterized by frequent drug-resistant seizures, cerebral visual impairment, motor dysfunction, and sleep and gastrointestinal disturbances. Preliminary evidence suggests that highly purified cannabidiol (CBD) may reduce seizure frequency, but data on its effects on comorbidities are lacking. This study aimed to evaluate the efficacy and safety of CBD in individuals with CDD.

Methods: We conducted a prospective, open-label, single-center study including patients with CDD aged >1 year. Outcomes included motor seizure frequency, caregiver- and clinician-rated Clinical Global Impression (CGI), and changes in sleep, motor abilities, and EEG at 3, 6, and 12 months. CBD plasma levels were measured with High-Performance Liquid chromatography-Mass Spectrometry (HPLC-MS).

Results: Eight of nine patients (all females; median age 10 years, range 1-24) completed the study, with a retention rate at 12 months of 8/9 (89%). One discontinued at 6 months due to a skin rash. A > 50% seizure reduction was observed in 8/9 patients at 3 months, 6/9 at 6 months, and 1/8 at 12 months. Seven patients showed some degree of vigilance improvements, three in motor performance, and two in sleep and constipation. All caregivers reported at least minimal overall improvement (CGI score 3) at 3 months, and three reported marked improvement (CGI score 2), with a peak at 3 months. Five patients showed adverse events during the trial, but none were considered serious. The median CBD dose at all time-points was 15.6 mg/kg/day (IQR 10.0-18.9) corresponding to a plasma dose of 69.9 ng/mL (IQR 29.8-114.6) and the median concentration/dose ratio was 4.7 (IQR 2.7-6.8).

Significance: The safety and efficacy of highly purified CBD in CDD were consistent with previous reports in the literature, with possible benefits beyond seizure control. Further studies are warranted to assess non-seizure outcomes and compare long-term efficacy across treatment options.

Plain language summary: We studied nine girls with CDKL5 deficiency disorder who had frequent, hard-to-treat seizures. They received cannabidiol for up to 1 year, added to their usual medicines. Most children had fewer seizures in the first months of treatment. Some families also noticed better alertness, eye contact, movement, sleep, or constipation. Side effects were usually mild and manageable. Although seizure frequency often returned to baseline by the end of the study, most families chose to continue cannabidiol. Because this was a small study without a placebo group, these results are preliminary, and larger controlled trials are needed.

Objective: Memory dysfunction is a common disabling comorbidity in temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). While bilateral fornix diffusion abnormalities have been reported in TLE using diffusion tensor imaging (DTI), the impact of fornix pathology on cognitive outcomes remains unclear. This study investigated the relationships between fornix DTI, hippocampal volume, and cognitive outcomes in TLE.

Methods: Thirty-five TLE patients (21 unilateral HS, 11 non-HS, 3 bilateral HS) and 22 controls underwent fornix FLAIR-DTI (1.2 × 1.2 × 2 mm³ resolution) and hippocampal DTI (1 × 1 × 1 mm³) scans. Deterministic tractography was used to extract left and right fornix diffusion metrics including fractional anisotropy (FA). Whole hippocampi were manually segmented to yield volume and mean diffusivity (MD). In a subset of 23 TLE patients, linear correlations were assessed for verbal memory, non-verbal memory, and processing speed index (PSI) versus imaging measurements.

Results: In the HS group, a significant linear correlation was found between both hippocampal volume (r = 0.58, p = 0.001) and MD (r = -0.42, p = 0.03) with fornix FA. Left hippocampal volume correlated with verbal memory (r = 0.74, p = 0.0001) but not with PSI (p > 0.05). Left fornix FA also correlated with verbal memory (r = 0.48, p = 0.025). In contrast, right hippocampal volume and right fornix FA showed no correlation with non-verbal memory (p > 0.05). FA of both left and right fornix correlated with PSI (left: r = 0.45, p = 0.038; right: r = 0.44, p = 0.037).

Significance: The findings of correlations between the hippocampus and memory, but not processing speed, and fornix with both memory and processing speed in TLE suggest a specialized role of the hippocampus in memory and a broader role for the fornix in cognitive function, beyond its association with memory.

Plain language summary: The hippocampus is a brain structure involved in learning and memory. Patients with temporal lobe epilepsy (TLE), especially those with damage to the hippocampus, often experience memory and thinking problems. This study used advanced brain magnetic resonance imaging (MRI) to explore the role of a nearby structure called the fornix, which connects the hippocampus to other brain areas. We found that damage to both the hippocampus and fornix was linked to poor verbal memory, while damage to the fornix also affected thinking speed. These findings suggest that the fornix plays a broader role in brain function than previously thought.

Objective: Sialidosis 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).

Methods: We 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.

Results: Therapeutic 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.

Significance: Prospective documentation of clinical course and treatment outcomes-ideally through an international registry-is crucial to improve patient care and inform therapeutic strategies.

Plain language summary: Sialidosis 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.

Objective: To evaluate whether scalp oscillatory patterns-particularly scalp fast oscillations (SFOs) (>30 Hz) detected using 256-channel high-density EEG (HD-EEG)-are associated with and can predict surgical outcomes in patients with drug-resistant temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) undergoing anterior temporal lobectomy (ATL).

Method: This prospective cohort study included 47 patients with drug-resistant TLE-HS who underwent HD-EEG and subsequent ATL with at least 24 months of postoperative follow-up. A total of 70 averaged interictal epileptiform discharges (IEDs) were analyzed using time-frequency methods. Scalp oscillation frequencies across anterior temporal, posterior temporal, and extratemporal regions were calculated, and cluster analysis was performed to identify significant patterns. Scalp fast oscillations (SFOs; >30 Hz) were separately analyzed. Associations with surgical outcomes were assessed using generalized linear mixed models, and diagnostic performance was evaluated.

Results: A total of 70 averaged IEDs from 47 patients were analyzed. Patients with seizure recurrence exhibited higher median scalp oscillation frequencies across anterior temporal (34.26 Hz), posterior temporal (29.47 Hz), and extratemporal regions (25.25 Hz) compared to seizure-free patients (12.50, 7.56, and 9.17 Hz, respectively). Among 22 IEDs with SFOs (>30 Hz), cluster-based analysis identified a specific frequency pattern significantly associated with surgical outcome (p = 0.031). This SFO-based pattern independently predicted seizure recurrence (odds ratio = 12.60, 95% CI: 1.19-133.89, p = 0.036), with a sensitivity of 87.5%, specificity of 64.3%, and an area under the receiver operating characteristic curve of 0.759.

Significance: This study demonstrates that specific scalp oscillatory patterns, particularly SFOs detected via 256-channel HD-EEG, are predictive of surgical outcomes in TLE-HS. These findings suggest that scalp oscillation analysis may serve as a valuable, noninvasive biomarker in the presurgical evaluation of epilepsy and could aid in delineating the extent of the epileptogenic network.

Plain language summary: In this study, we used advanced brainwave recordings (called high-density EEG) to examine electrical patterns in the brains of people with epilepsy. We found that certain fast brainwave signals were linked to whether surgery could stop seizures. These signals may help doctors better plan epilepsy surgery in the future.

Objective: Stigma remains a major determinant of impaired quality of life (QoL) in people with epilepsy (PwE). We aimed to investigate perceptions of epilepsy-related stigma in the Italian general population, assess knowledge of epilepsy and seizure first aid, and identify factors associated with stigmatizing attitudes.

Methods: We conducted a cross-sectional, anonymized online survey using a structured questionnaire. The instrument comprised four sections: (1) sociodemographic characteristics; (2) epilepsy-related knowledge and perceptions; (3) seizure first aid (12 items on correct and incorrect actions during a seizure, summarized into the Seizure First Aid Knowledge Score (SAFE score - range 0-12); and (4) stigma assessment using the validated Stigma Scale of Epilepsy (SSE). Multivariate linear regression was used to explore predictors of stigma.

Results: A total of 1159 individuals completed the survey (mean age 36.9 ± 16.2 years; 64.6% women). SSE demonstrated excellent internal consistency (Cronbach's α = 0.89-0.90). Women reported higher stigma than men (53.1 ± 16.8 vs. 48.6 ± 17.6; p < 0.001). Participants from Southern Italy had significantly higher SSE scores compared to Central or Northern regions (53.4 ± 17.5 vs. 48.1 ± 16.4 and 49.8 ± 16.0; p < 0.001). Healthcare professionals reported lower stigma compared with PwE, relatives, or individuals without epilepsy (47.6 ± 17.2 vs. 55.6 ± 18.1, 51.8 ± 16.0, and 52.0 ± 17.2; p = 0.023). A higher SAFE score was inversely associated with stigma (β = -0.89, p = 0.013). Although most participants recognized appropriate first aid measures, misconceptions persisted: 38.1% endorsed inserting hands into the mouth during seizures, and 24.5% considered physical restraint appropriate.

Significance: Stigma persists in Italy, particularly among women and residents of Southern regions. Tailored educational interventions may both improve seizure safety and mitigate stigma, ultimately enhancing QoL for PwE.

Plain language summary: Epilepsy is often associated with negative attitudes that can affect the well-being of people living with the condition. In this study, we surveyed adults across Italy to understand how epilepsy is perceived, how much people know about seizure first aid, and how stigma varies across different groups. We found that stigma remains common, especially among women and people living in Southern Italy, while better knowledge of how to help during a seizure was linked to lower stigma. These results highlight the importance of public education to improve understanding, safety, and social inclusion.

Purpose: Continuous electroencephalogram (cEEG) monitoring is an important technique used in detecting electroclinical seizures in the pediatric intensive care unit (PICU). This study developed an artificial intelligence method for the real-time automatic detection of seizures in the PICU.

Methods: We designed an artificial intelligence method to analyze EEG, electromyography (EMG), and electrocardiography (ECG) signals, detecting features from multiple dimensions, extracting candidate signal fragments in real time, and analyzing the relevant indicators of these fragments to determine whether they indicate electroclinical seizures. We tested the sensitivity and specificity of the detection system on patients with seizures who were hospitalized in the PICU of Peking University First Hospital and received cEEG monitoring.

Results: A total of 28 PICU patients were collected, including 17 boys and 11 girls, with a median age of 4.30 (1.02-7.00) years. Sixteen patients had convulsive status epilepticus, of which eight were generalized and eight were focal. Twelve patients had cluster seizures, of which seven were generalized and five were focal. A total of 218.73 h of EEG data were collected from all 28 EEG records. The electroencephalography physician annotated a total of 1561 seizures, whereas the algorithm detected a total of 1095 seizures. The overall detection sensitivity was 94%, and the overall false detection rate was 0.18 (0.03-0.28)/h. There was no statistical difference in the sensitivity and false detection rate between focal and generalized seizures.

Conclusion: The detection system has high sensitivity and specificity, suggesting great potential for future real-time automatic detection of electroclinical seizures in the PICU.

Plain language summary: We developed a computer program that helps doctors quickly detect seizures in critically ill children by analyzing brain activity, muscle movements, and heart rate signals. The system was designed specifically for the challenging environment of pediatric intensive care units, where timely seizure detection is particularly important but often difficult. The program reliably identified seizures that showed both brain activity and physical signs, matching doctors' diagnoses. This technology marks an important step toward better monitoring and care for critically ill children with seizures.

Objective: To quantify amygdala and hippocampal volumetric asymmetries in patients with drug-resistant epilepsy (DRE) and extra-medial temporal lesions (EMTLs) and to assess the prevalence of structural alterations relative to drug-resistant temporal lobe epilepsy (TLE), extratemporal lobe epilepsy (ETLE), and healthy individuals.

Methods: Retrospective cross-sectional study of 298 participants evaluated at the NIH Clinical Center (2004-2023), including 252 patients with focal DRE and 46 healthy volunteers. Of the DRE cohort, 63 had lateralized EMTL (48 left, 15 right). High-resolution brain MRIs were segmented and analyzed to obtain normalized amygdala and hippocampal volumes. An asymmetry index (AI) assessed directionality, and absolute AI measured magnitude. Atrophy and hypertrophy were defined relative to healthy medians using robust dispersion thresholds. Group comparisons incorporated correction for multiple testing.

Results: Dual pathology with mesial temporal sclerosis was radiologically identified in 20.6% of EMTL cases, predominantly ipsilateral. Adjusted amygdala and hippocampal volumes did not differ significantly across groups, and consistent amygdala atrophy was not observed. Left EMTL showed increased hippocampal asymmetry magnitude and a 39.6% prevalence of ipsilateral hippocampal atrophy, comparable to left TLE (34%). Right EMTL showed loss of the physiologic left-smaller-than-right hippocampal pattern, with hypertrophy in the right amygdala (40%), left amygdala (46.7%), and contralateral hippocampus (40%), as well as ipsilateral hippocampal atrophy in 26.7%.

Significance: We found mesial temporal volumetric changes in a significant proportion of EMTL patients. Directional, magnitude, and outlier-based analyses help disentangle coexisting atrophy and hypertrophy, revealing potential compensatory network-level changes in EMTL-associated DRE not previously identified.

Plain language summary: This study looked at changes in two brain structures, the amygdala and hippocampus, in people with treatment-resistant epilepsy associated with lesions outside the medial temporal lobe. We found that patients with lesions on the left side often had a small left hippocampus, while those with right-sided lesions showed more complex patterns, including enlargement of both the amygdala and left hippocampus and less frequent small right hippocampus. These findings suggest that detailed measurements of brain asymmetry can uncover changes missed by standard assessment and may help doctors better locate seizure activity and plan treatments.