BACKGROUND:Variants in GABAA-receptor subunits genes are linked to neurodevelopmental disorders and epilepsy, but genotype-phenotype correlations remain unclear. This study aims to describe the clinical characteristics of children with epilepsy harboring such variants and explore these correlations. METHODS:Trio-WES/WES results from 886 individuals with unexplained epilepsy, evaluated between January 2018 and December 2023, were reviewed. Six patients with pathogenic or likely pathogenic variants in GABAA-receptor subunit genes (GABRA1, GABRG2) were included. Clinical phenotype, treatment, and genotype were analyzed. RESULTS:Four GABRA1 and two GABRG2 variants were identified in six unrelated families. Three variants (GABRA1 p.R159G, GABRG2 p.G273X, and GABRG2 p.R446Lfs*10) were novel. Computational predictions suggested these variants alter protein structure and impair receptor function. Clinically, four patients had developmental and epileptic encephalopathy and two had genetic epilepsy with febrile seizures plus. One patient had drug-resistant epilepsy, while the other five achieved stable seizure control with treatment,most commonly with valproate and levetiracetam. CONCLUSION:Clinical phenotypic heterogeneity in epilepsy associated with GABAA receptor variants is significant and may relate to variant type and location. This study expands the spectrum of known pathogenic variants in a Chineses cohort and provides a reference for clinical diagnosis and genetic counseling. The findings underscore the need for large-scale collaborative studies to further refine genotype-phenotype correlations.

OBJECTIVE:To investigate risk factors affecting the short- and long-term prognosis of pediatric status epilepticus (SE) complicated by nonconvulsive status epilepticus (NCSE) during the disease course and to analyze the clinical heterogeneity of this group to effectively identify population characteristics and subgroups influencing prognosis. METHODS:This study is a single-center retrospective cohort study. Clinical data from 215 pediatric patients diagnosed with SE at Chongqing Medical University Children's Hospital between February 2005 and September 2024, who met the diagnostic criteria for NCSE during their illness, were included. Univariate analysis and multivariate logistic regression were employed to identify factors associated with short-term and long-term adverse outcomes. Hierarchical cluster analysis was conducted based on clinical characteristics. RESULTS:The in-hospital mortality rate was 3.3% (7/215), increasing to 6.0% (12/200) in long-term follow-up. The short-term poor prognosis rate was 29.8% (64/215), while the long-term poor prognosis rate was 20.5% (41/200). Multivariate analysis revealed that independent risk factors for poor short-term prognosis included GCS scores of 3-8, global developmental delay, interictal EEG showing periodic discharges, and diffuse MRI abnormalities. Poor long-term prognosis was primarily associated with GCS scores of 3-8, global developmental delay, and electroclinical syndromes. Further clinical phenotype clustering analysis revealed four heterogeneous subgroups: super-refractory subgroup (characterized by profound impaired consciousness and diffuse brain injury), young-age metabolic subgroup (age < 24 months with multifocal abnormalities), focal structural subgroup (manifesting as focal neurological deficits and structural etiology), and benign reactive subgroup (mild altered consciousness and treatment sensitivity). SIGNIFICANCE:Level of consciousness, electroencephalogram (EEG), neurodevelopmental status, and electroclinical syndromes can serve as core indicators for prognostic stratification in children with NCSE; subtyping based on clinical features can effectively distinguish heterogeneous subgroups, providing a clinical phenotypic basis for individualized stratified diagnosis, treatment, and prognostic assessment of pediatric NCSE, thereby addressing the current lack of a multidimensional stratification framework in clinical practice.

OBJECTIVE: To compare the genotype-phenotype relationships betweenchildren with PRRT2 gene variants and 16p11.2 microdeletion syndrome. METHODS: A retrospective analysis was performed on clinical data from 68 patients with PRRT2 variants and 16 patients with 16p11.2 microdeletionsyndrome at the Children’s Hospital of Chongqing Medical Universitybetween February 2015 and August 2024. Genetic testing included whole-exome sequencing and copy number variation sequencing. RESULTS: (1) PRRT2 Cohort (n=68): Clinical diagnoses included benign familial infantile epilepsy (49/68), paroxysmal kinesigenic dyskinesia (4/68),infantile convulsions with paroxysmal choreoathetosis (8/68), and otherepilepsy subtypes (7/68). Genetic analysis revealed frameshift variants in 89.7% (61/68), with c.649dupC as the predominant mutation(penetrance:77.2%). Electroencephalography detected epileptiformdischarges in 45.6% of cases. Brain MRI showed nonspecific abnormalities,including widened extra-axial spaces (75%). Oxcarbazepine showed bettertherapeutic efficacy than levetiracetam. (2) 16p11.2 microdeletion cohort (n=16): This group exhibited moresevere phenotypes: The incidence of persistent status epilepticus may behigher (18.8% vs 2.9%, P=0.045, q=0.084), with 87.5% being de novovariants and 81.2% having negative family history. Compared with the PRRT2 group, these patients had significantly increased risks of congenitalheart disease, global developmental delay, and structural brainabnormalities (all P < 0.05). CONCLUSION: PRRT2-related disorders are characterized by incompletepenetrance and benign clinical courses, whereas 16p11.2 microdeletionsyndrome manifests complex phenotypic spectra due to polygenicinvolvement, necessitating distinct diagnostic and therapeutic strategies.

INTRODUCTION:The aims of this study were to synthesize population-based studies of epilepsy prevalence published between 1980 and 2025, estimate pooled global prevalence, characterize regional differences, quantify temporal trends, and examine the influence of study characteristics and development indicators (Human Development Index [HDI] and Socio-Demographic Index [SDI]). METHODS:We systematically searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Library for observational studies published from January 1, 1980, to December 31, 2025. Random-effects meta-analysis was used to pool prevalence estimates. Pre-specified subgroup analyses were conducted by geographical region, survey period, study design, data source, sample size, and HDI/SDI strata. Methodological subgroup analyses and sensitivity analyses were further performed to assess the robustness of the pooled estimates. Temporal patterns were assessed using regression-based β trend analysis across study survey years and estimated annual percentage change (EAPC) derived from the Global Burden of Disease (GBD) database. RESULTS:We included 216 studies comprising 278,651,975 participants and 2,114,157 epilepsy cases. The pooled global prevalence was 7.57 per 1,000 population (95% confidence interval [CI], 6.78-8.45). Literature-based trend analysis suggested an increase in reported prevalence estimates from 1980 to 2025 (β = 0.206 per 1,000 population per year; p < 0.01). GBD-based analyses also showed an overall increase from 1990 to 2021 (EAPC = 0.102% per year), with significant increases during 1990-2009 but no significant change during 2010-2021. Prevalence differed significantly across geographical regions (p < 0.001), highest in Africa (10.67 per 1,000) and lowest in Asia (5.20 per 1,000). Prevalence was higher in low-HDI settings than in very high-HDI settings, but meta-regression did not support significant linear associations between prevalence and HDI or SDI (both p > 0.05). No significant sex difference was observed (p = 0.76). Sensitivity analyses supported the robustness of the main pooled estimate, and methodological subgroup analyses showed no major variation across prevalence definitions, case ascertainment methods, or diagnostic confirmation approaches. CONCLUSIONS:Epilepsy prevalence remains high worldwide, with an overall increase in reported prevalence over the past 4 decades but a slower recent rise. Marked geographical disparities were observed, with higher reported prevalence in low-resource settings. Strengthening standardized epidemiological surveillance and improving access to diagnosis and treatment remain priorities, particularly in resource-limited regions.

BACKGROUND:Children with spike-wave activation in sleep (SWAS) face significant neurodevelopmental impairments, including cognitive deficits, oropharyngeal dysfunction and attention-deficit/hyperactivity disorder (ADHD). While SWAS is a known contributor, the impact of specific clinical factors and the comparative efficacy of treatments like ketogenic diet (KD), steroids, and benzodiazepines (BZDs) on outcomes remain unclear. METHODS:This retrospective cohort study analyzed 134 children with SWAS treated at Children's Hospital of Chongqing Medical University (2015-2024). Clinical data, electroencephalograph, neurodevelopmental assessment, and treatment response were collected. RESULTS:Treatment included KD (n = 11), steroids (n = 72), BZDs (n = 105, including a high-dose diazepam subgroup n = 5), and antiseizure medication (ASM) adjustments (n = 275). Higher seizure frequency correlated significantly with increased cognitive impairment (P < 0.05), oropharyngeal dysfunction (P < 0.05), ADHD (P < 0.05), and relapse rate (P < 0.05). Earlier seizure onset and SWAS onset predicted higher relapse. Structural abnormalities were associated with earlier seizure onset (P < 0.05) and greater cognitive impairment (P < 0.05). Relapse correlated with earlier onset and higher oropharyngeal dysfunction/ADHD (P < 0.05). Treatment response rates were: KD 81.8% (9/11), steroids 65.3% (47/72), BZDs 47.6% (50/105), ASM adjustments 18.9% (52/275). High-dose diazepam (0.5-1.0 mg/kg/day) achieved 80% (4/5) response. KD, steroids, and BZDs were significantly more effective than ASM adjustments (P < 0.05). CONCLUSIONS:Seizure frequency is a critical modifiable predictor of neurodevelopmental impairment and relapse in SWAS, independent of SWAS burden. Structural etiology increases cognitive impairment risk. KD demonstrates efficacy for Spike-Wave Index reduction, comparable to steroids and BZDs, with no statistically significant intergroup differences. High-dose diazepam shows promise for refractory cases. ASM adjustments, while less effective for Spike-Wave Index, offer practical seizure control.

Tumor Treating Fields (TTFields), as an emerging non-invasive therapeutic approach, has gradually demonstrated its potential as an adjuvant therapy in cancer treatment in recent years. Currently, TTFields has become an important adjunct to the standard treatment of glioblastoma (GBM). Real-world data on its clinical application, outcomes, and prognostic factors hold significant value for optimizing clinical practice. This study aims to evaluate the actual effectiveness of TTFields in treating GBM by providing clinical data and exploring potential clinical factors that may influence its efficacy. This study is a retrospective cohort study that included 40 newly diagnosed glioblastoma (ndGBM) patients received TTFields treatment based on the Stupp regimen. Additionally, 48 ndGBM patients who did not receive TTFields treatment during the same period were selected as the control group through continuous sampling. Kaplan-Meier curves were employed to estimate the overall survival (OS) and progression-free survival (PFS) in both groups. To identify factors affecting these outcomes and the efficacy of TTFields, a Cox regression analysis was subsequently performed on various clinical variables. Patients receiving the TTFields demonstrated superior median PFS (12.0 months, 95

OBJECTIVE:To investigate age-dependent mechanisms of silent-synapse transformation and their contribution to hippocampal circuit reorganization following convulsive brain injury induced by status epilepticus (SE). METHODS:Three-week-old (juvenile) and eight-week-old (adult) C57BL/6J mice were used. SE was induced by intraperitoneal kainic acid (KA). Hippocampal assessments were performed at 3 days (acute phase) and 28 days (chronic phase) post-SE. Dendritic spines in the dentate gyrus (DG) were visualized by Dil staining and confocal imaging to quantify total density and subtype distributions. Western blot was used to measure hippocampal expression of AMPA receptor subunits (GluA1-GluA4), NMDA receptor subunits (GluN1, GluN2A, GluN2B), and PSD95. Surface synaptic localization of GluA1 in CA1 was further evaluated by immunofluorescence staining and multi-threshold colocalization quantification with Synapsin. Whole-cell patch-clamp recordings were performed to determine the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in CA1. Correlation analyses were conducted to examine the association between DG filopodia density and CA1 sEPSC frequency during the acute phase. RESULTS:(1) After SE, juvenile mice exhibited increased densities of mushroom and stubby spines at both time points (P < 0.01) accompanied by a reduction in filopodia density (P < 0.01). In contrast, adult mice showed decreased mushroom spine density (P < 0.01) with increased filopodia formation during the acute phase (P < 0.01). (2) In the juvenile group, the expression levels of GluA1, GluA4, GluN2A, GluN2B, and PSD95 in the hippocampus were significantly elevated during the acute phase after SE. By the chronic phase, GluA3 expression remained upregulated while GluA4 was downregulated, and GluN2A/GluN2B remained persistently increased. In adults, GluA1 was decreased and GluA4 increased during the acute phase. GluN1 remained elevated across both phases, and GluN2A increased selectively in the chronic phase. PSD95 upregulation in adults was observed only in the chronic phase. Immunofluorescence analysis further corroborated the biochemical findings by showing increased surface synaptic GluA1 colocalization with Synapsin in CA1 at 3 days post-SE in juveniles, but decreased colocalization in adults. (3) Electrophysiological assessment revealed that the juvenile group showed increased sEPSC frequency (P < 0.05) and decreased amplitude (P < 0.01), whereas adults exhibited reduced sEPSC frequency (P < 0.05) without a significant change in amplitude. (4) Correlation analyses revealed a strong negative association between DG filopodia density and CA1 sEPSC frequency at 3 days post-SE in both age groups (juveniles: r = -0.908, p = 0.033; adults: r = -0.964, p = 0.036), indicating an age-dependent but coordinated structure-function coupling across hippocampal subregions during the acute post-SE period. CONCLUSIONS:SE bidirectionally modulates silent synapse transformation in an age-dependent manner. The juvenile brain adapts to pathological stimuli induced by SE through rapid conversion of silent synapses into functional mature synapses. In contrast, the adult brain exhibits reduced synaptic maturity and suppressed synaptic function, which may exacerbate post-epileptic neural network dysfunction.

OBJECTIVE:To analyze the current state of primary pediatric epilepsy care, providing evidence for regional capacity-building strategies. METHODS:The cross-sectional survey design was adopted to assess the epilepsy diagnostic and therapeutic capabilities of pediatric physicians from 37 medical institutions in the nine main urban districts and surrounding counties of Chongqing. RESULTS:Tertiary (56.8%, 21/37) and general hospitals (75.7%, 28/37) dominated healthcare, yet pediatric neurology lagged: only 48.7% (18/37) had dedicated teams. Key technologies like Video-EEG (43.2%) and genetic testing (54.1%) were underutilized; novel therapies (ketogenic diet 13.5%, neuromodulation 8.1%) were rarely applied. The median annual outpatient volume was 50 cases, and 33.3% of hospitals achieved >50% seizure freedom rate, yet 20.8% had >15% treatment inefficacy. Evident deficiencies of physician training: 52.4% (87/166) lacked systematic epilepsy training, and only 1.2% (2/166) had passed advanced EEG certification, resulting in only 19.3% (32/166) fully mastering epilepsy classification systems, while 31.9% demonstrated medication selection errors. Significant discrepancies in clinical decision-making: 18.7% (31/166) of physicians inappropriately selected carbamazepine for juvenile absence epilepsy, while 3.6% (6/166) adopted a high-risk immediate medication switching strategy. Fragmented patient management: 8.4% of physicians did not provide health education, and 59.0% (98/166) cited poor family adherence due to insufficient disease awareness. The regional referral rates varied widely (median: 17.5%, IQR: 35-5%). SIGNIFICANCE:Tertiary hospitals undertake the main clinical burden but lack the construction of specialized infrastructure; lagging staff training leads to undermining the standardization of diagnosis and management; and the problem of the lack of systematic solutions in patient management persists. To enhance the overall service delivery, there are some proposed solutions including establishing hierarchical diagnosis and treatment networks, enhancing specialist training, and implementing regional quality control systems.

INTRODUCTION:The mTOR inhibitors sirolimus and everolimus are targeted therapies for tuberous sclerosis complex (TSC). Recent studies suggested their potential efficacy in treating epilepsy in TSC children. However, clinical evidence remains limited, and reports of adverse effects vary widely. This study aims to investigate the efficacy and safety of mTOR inhibitors in reducing epileptic seizures in TSC children. METHODS:We retrospectively analyzed the clinical data of children with TSC. Children were categorized into groups based on the use of mTOR inhibitors. Seizure frequency and adverse effects were monitored, and a ≥ 50 % reduction in seizure frequency was defined as a treatment response. Subgroup analyses were conducted for children with seizure onset age ≤2 years and >2 years, respectively. Additionally, the study compiled adverse effects and abnormal laboratory findings potentially associated with mTOR inhibitors. RESULTS:Among 104 TSC children with epilepsy, 53 were treated with mTOR inhibitor (mTORi group), 51 were not treated with mTOR inhibitor (No mTORi group). In the mTORi group, 81.1 % of children responded to treatment, significantly higher than the 54.9 % response rate in the No mTORi group (P = 0.004). Children treated with sirolimus (79.4 %) demonstrated a significantly higher response rate compared to those not receiving mTOR inhibitors (P = 0.021). In the subgroup with seizure onset ≤2 years, the response rate was significantly higher in the mTORi group than in the no mTORi group (73.5 % vs. 50.0 %, P = 0.049). Similarly, in the subgroup with seizure onset >2 years of age, the response rates between the two groups (94.7 % vs. 63.2 %) showed a significant difference (P = 0.042). In both subgroups, longer duration of mTOR inhibitor treatment was associated with higher response rates. Multivariate logistic regression analyses in both subgroups demonstrated that mTOR inhibitors are independent protective factors for antiepileptic treatment response in children (P < 0.05). Among the 98 children treated with mTOR inhibitors, 48 (49.0 %) experienced adverse effects, including four children (4.1 %) experienced Grade 3 adverse effects. Sirolimus and everolimus exhibited comparable safety profiles. The incidence of adverse effects among children who began mTOR inhibitor therapy before age 2 reached 62.5 %, significantly higher than the 42.4 % observed in children who started after age 2. CONCLUSION:Adjunctive therapy with mTOR inhibitors improves the response rate to antiepileptic treatment in children with TSC, with sirolimus and everolimus demonstrating comparable efficacy. Therapeutic benefits were observed regardless of seizure onset age, and longer treatment duration was associated with greater efficacy. mTOR inhibitors may cause some adverse effects in children, but most are relatively mild.

BACKGROUND:To evaluate the efficacy and safety of adjunctive perampanel (PER) in young children with drug-resistant epilepsy (DRE) aged 7-46 months, and to identify predictors of treatment response in real-world clinical practice. METHODS:We conducted a nonrandomized, open-label, single-arm, self-controlled real-world study at the Children's Hospital of Chongqing Medical University between December 2020 and August 2024. Eighty-seven children with DRE received PER as adjunctive therapy to existing antiseizure medications (ASMs). The primary endpoint was the responder rate (≥ 50% reduction in seizure frequency) at 3, 6, 9, and 12 months. Secondary endpoints included seizure freedom, treatment retention, and treatment-emergent adverse events (TEAEs). RESULTS:Responder rates were 39.5%, 46.9%, 43.2%, and 44.4% at 3, 6, 9, and 12 months, respectively. Responder rates were 50.0% in Dravet syndrome, 50.0% in Lennox-Gastaut syndrome, and 34.8% in infantile epileptic spasms syndrome. Children with genetic etiologies had a 51.7% responder rate, including 60.0% in those with SCN1A variants. Multivariable logistic regression identified perinatal brain injury as an independent predictor of favorable response, while concomitant use of three ASMs predicted poorer outcomes. Treatment retention rates were 87.4%, 69.0%, 59.8%, and 55.2% at 3, 6, 9, and 12 months. TEAEs occurred in 23.0% of patients, most commonly somnolence (11.5%) and irritability/aggressive behavior (9.2%); 4.6% discontinued due to TEAEs. CONCLUSION:Adjunctive PER demonstrated clinically meaningful efficacy and a favorable safety profile in young children with DRE, supporting its potential role as a broad-spectrum ASM in this age group.

Objective: To investigate the early predictive value of neutrophil-to-lymphocyte ratio (NLR) for surgical requirement in infants with traumatic subdural effusion (TSE).Methods: A single-center retrospective cohort study was conducted, enrolling 629 patients aged ≤6 months with isolated traumatic brain injury. NLR was calculated based on a complete blood count within 48 hours post-injury. Logistic and LASSO regression were used to screen for independent risk factors. Machine learning was employed to impute missing values for continuous variables. The association between NLR and subdural burr hole drainage was analyzed using the area under the receiver operating characteristic curve (AUC). Combined prediction models were constructed.Results: 52 cases (8.27%) required surgical intervention. Injury mechanism, seizure (P<0.001), shortened APTT (original P=0.02, after imputation P=0.03), and elevated NLR (original P=0.01, after imputation P=0.004) were independent risk factors for surgical requirement. The optimal cutoff value for NLR was 0.80 (original apparent AUC=0.73, after imputation cross-validated AUC=0.69). The surgery rate in the high-NLR group (≥0.80) (13.70%) was significantly higher than that in the low-NLR group (4.18%) and was more frequently associated with traffic accident injury (20.00% vs. 9.75%) and seizure (16.30% vs. 6.41%). The model combining NLR with injury mechanism, seizure, and APTT significantly improved predictive performance (original apparent AUC=0.84, after imputation cross-validated AUC=0.78).Conclusion: NLR, as a low-cost and available biomarker, can effectively predict surgical requirements in infants with TSE. When combined with clinical indicators, it significantly enhances risk stratification capability. Machine learning handling missing data can improve the reliability of predictive models.

OBJECTIVE:To evaluate the real-world effectiveness and safety of adjunctive zonisamide in children with developmental epileptic encephalopathy/epileptic encephalopathy (DEE/EE), focusing on younger children and highly drug-resistant cases. METHODS:This open-label, nonrandomized, self-controlled, real-world study included 127 children with DEE/EE at a single center from 2020 to 2025. The primary endpoint was the responder rate (≥ 50% seizure reduction) at 3, 6, 9, and 12 months, analyzed using last observation carried forward. Secondary endpoints included seizure freedom, retention, and adverse events (AEs). Multivariable analysis identified predictors of efficacy. RESULTS:Responder rates were 51.2%, 55.3%, 53.7%, and 53.7% at 3, 6, 9, and 12 months, respectively. Seizure-free rates were 23.6%, 26.8%, 24.4%, and 27.6%. Efficacy was consistent across age and etiology. Female gender (OR = 3.00) and fewer prior anti-seizure medications (OR = 0.77) independently predicted 12-month response. Among children failing ≥ 5 prior medications, 44.3% responded, and 20.0% achieved seizure freedom. The 12-month retention rate was 81.9%. AEs occurred in 14.2%, most commonly reduced appetite (7.9%); most were tolerable. CONCLUSION:Adjunctive zonisamide provides sustained efficacy and favorable tolerability in children with DEE/EE, including young children < 6 years and highly drug-resistant cases. Gender and prior treatment history predict long-term efficacy, supporting its reliable risk-benefit profile for refractory epilepsy.

Objective: To analyze genotype-phenotype correlations in patients with KCNMA1 variants and functionally characterize two unreported missense variants: c.853A>T (p.I285F) and c.3196G>A (p.G1066R). Methods: We retrospectively reviewed clinical data from six pediatric patients with KCNMA1 variants. Protein structural modeling and cross-species conservation analysis were performed. HEK293T cells were transfected with wild-type or mutant BK channel constructs. Channel function was assessed using whole-cell patch-clamp electrophysiology to measure current amplitude, current density, and voltage/Ca²⁺sensitivity. Protein expression was evaluated by Western blot analysis of total and membrane fractions. Results: (1) Five patients presented with epileptic seizures, including myoclonic, focal motor/non-motor, generalized tonic-clonic, and atonic seizures; two exhibited drug resistance. Paroxysmal nonkinesigenic dyskinesia (PNKD) was observed in two patients. All five patients with epilepsy demonstrated language impairment or global developmental delay. (2) The residues affected by the mutations, I285 and G1066, are highly conserved across species. Protein three-dimensional structure predictions revealed alterations in the number and distance of hydrogen bonds for both mutations. (3) Under low Ca²⁺ (1 μM), the p.I285F variant significantly reduced BK current amplitude (p < 0.05) and current density across the 50–150 mV range. At high Ca²⁺ (10 μM), current density was increased in the hyperpolarized range (-50 to 0 mV) compared to wild-type. The half-activation voltage (V₁/₂ ) was significantly left-shifted at 1 μM Ca²⁺ (p < 0.05), while the slope factor (k) remained unchanged. (4) At both 1 μM and 10 μM Ca²⁺, p.G1066R did not alter BK current amplitude. However, at 10 μM Ca²⁺, current density at 0 mV was significantly lower than wild-type (p < 0.05). The I-V curve was right-shifted, while V₁/₂ and k values remained unchanged. (5) Total protein levels of both p.I285F and p.G1066R were significantly lower than wild-type (p < 0.05), whereas membrane protein expression did not differ significantly (p > 0.05). Conclusion: KCNMA1 -related disorders commonly present with epilepsy, developmental delay, and PNKD3. p.I285F and p.G1066R are loss-of-function variants, impairing channel activity through reduced current amplitude, altered voltage sensitivity, and lower total protein expression, supporting their pathogenicity.

BACKGROUND:In recent years, advancements in sequencing technology have led to a progressive increase in the proportion of epilepsy cases with genetic etiology, while simultaneously facilitating the ongoing identification of epilepsy-associated genes. To summarize the genotype-phenotype association of epilepsy patients is of great significance for the interpretation of genetic reports, clinical diagnosis and treatment and genetic counseling. METHODS:We reviewed and analyzed the trio-WES/WES results of 886 patients with unexplained epilepsy. Ultimately, 288 epilepsy patients were included in this study. The clinical phenotype, treatment and genotype of the patients were analyzed. The single nucleotide variations in all samples were explained. RESULTS:Of the original 886 patients with epilepsy with no identified cause, 288 patients were shown to have a genetic abnormality, yielding a WES diagnostic rate of 32.5%. The patients with onset before 2 years of age were more likely to have accompanying developmental delay (p=0.001). A total of 312 pathogenic/likely pathogenic variants involving 125 genes were detected. The most common genes affected were primarily SCN1A. After the pathogenic gene was identified, at least 16.7% more patients were able to use recommended medications. Patients with ion channel gene-related disorders had a significantly higher rate of receiving recommended medications. The CHRNA4, ATP1A2, SPTAN1, KCNMA1, and SCN9A, currently lack reports of incomplete penetrance related to epilepsy and our study suggests the potential for incomplete penetrance in these genes. CONCLUSION:This study summarized the clinical characteristics and genetic background of children with epilepsy, expanded the genotype-phenotype spectrum, and provided reference for genetic counseling and clinical diagnosis and treatment.

This study investigated dynamic brain network changes and their genetic correlations in children with idiopathic generalized epilepsy (IGE). We included 26 children with IGE and 35 healthy controls, all participants underwent resting-state functional magnetic resonance imaging and cognitive assessments. Modular variability (MV) in time-varying networks was compared, and correlations with cognition and clinical variables were analyzed, we also explored classification problems using machine learning. Gene sets associated with IGE-related network remodeling were identified using the Allen Human Brain Atlas and gene enrichment analysis tools. The results showed that children with IGE exhibited reduced MV in sensorimotor and frontoparietal networks and increased MV in the default mode network (DMN). MV changes in the left prefrontal and right orbitofrontal cortices correlated with verbal and full-scale IQ scores, respectively. MV changes in the left precuneus/posterior cingulate cortex correlated with performance IQ scores. Transcriptomic analysis revealed 985 genes (FDR < 0.05) whose spatial expression patterns covaried with network alterations, prominently enriched for synaptic signaling and neuroactive ligand-receptor interactions, including GABA receptor subunits (GABRE) and neurodevelopmental regulators (BCL11A). Machine learning confirmed MV as a significant predictor of verbal IQ (permutation P = 0.041), with DMN and frontoparietal regions contributing most to prediction. Dynamic brain network abnormalities in children with IGE were significantly associated with cognitive function and gene expression, providing new insights into the neural mechanisms underlying network dysfunction and cognitive impairment in epilepsy.

Background: Serum neurofilament light chain (sNfl), identified as a promising biomarker, is a protein released into the bloodstream post-axonal damage. Studies on its correlation with depression, however, remains scarce. The purpose of this study was to investigate the potential relationship between sNfL levels and risk of depression among a representative segment of the U. S. populace. Methods: This study included 1,909 participants from the 2013-2014 National Health and Nutrition Examination Survey. The 9-item Patient Health Questionnaire (PHQ-9 scale) assessed depression symptoms, while sNfl concentrations were measured using the Attelica fully automated immunoassay system. The logistic regression, restricted cubic splines (RCS), and subgroup analysis were performed to assess the relationship between sNfL, lnsNfL (log-transformed values of sNfl), and depression. Results: After adjusting for sociodemographic variables, lifestyle, and chronic conditions, sNfl and lnsNfL levels positively correlated with depression. A unit increase in sNfL and lnsNfL levels was linked to a 0.7 % and 33.8 % rise in depression risk, respectively [OR (95 % CI): 1.007 (1.000, 1.014), p = 0.041 for sNfl; 1.338 (1.015, 1.764), p = 0.039 for lnsNfl]. Additionally, a positive linear association was observed between lnsNfl levels and the risk of depression (p for overall = 0.039, p for nonlinear = 0.189 in RCS). No significant differences were observed across subgroups between lnsNfl and depression, with no significant impact on this relationship from subgroups (All p for interaction >0.05). Conclusion: The findings of our study suggest a significant positive correlation between sNfl and depression, warranting further investigation into the molecular dynamics linking sNfL to depression and subgroup variability.

BACKGROUND:The study analyzed the clinical features and risk factors for poor prognosis in children with Guillain-Barré syndrome (GBS) spectrum disorders positive for anti-sulfatide antibodies. METHODS:Clinical and follow-up data of 43 children diagnosed with GBS spectrum disorders positive for serum and/or cerebrospinal fluid anti-sulfatide antibodies and treated at the Children's Hospital of Chongqing Medical University between July 2018 and April 2023 were analyzed. A 1:1 matching was performed for a comparative analysis of clinical features. RESULTS:Respiratory tract prodromal infection was common in the positive anti-sulfatide antibody group (53.4%, 23 of 43). The main presenting symptoms were limb weakness (67.4%, 29 of 43), pain (67.4%, 29 of 43), ataxia (32.5%, 14 of 43), and cranial nerve involvement (62.8%, 27 of 43). The clinical classification was predominantly classical GBS (76.7%, 33 of 43), with a high prevalence of acute inflammatory demyelinating polyneuropathy (41.2%, 20 of 33). Brainstem and medulla lesions were the main cranial magnetic resonance imaging (MRI) findings (16.7%, six of 36), and spinal cord MRI (32.5%, 14 of 34) showed cauda equina or partial nerve root enhancement. The following features showed a significant difference in prevalence between the anti-sulfatide-antibody-positive and -negative groups: gender, cranial nerve involvement, nerve root tension sign, abnormal brain MRI, GBS disability score (GBS-DS) at discharge, difference in GBS-DS between admission and discharge, and GBS-DS at one-month follow-up. Shorter time to peak was identified as an independent risk factor for poor short-term prognosis in GBS spectrum disorders with positive anti-sulfatide antibodies. CONCLUSIONS:GBS spectrum disorders with positive anti-sulfatide antibodies have a relatively specific clinical phenotype. Shorter time to peak was an independent risk factor for poor prognosis.

Silver nanoparticles (AgNPs) have great potential in a broad range of applications because of their biochemical functionality, unique physical and optical properties. However, it is still a great challenge to synthesize small-size AgNPs with good stability and high performance for biosensors. In this work, triethanolamine and polyacrylic acid modified AgNPs (TEOA@AgNPs-PAA) with controllable size and high catalytic activity for sensitive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are reported. Monodisperse TEOA@AgNPs-PAA are prepared by the one-pot synthesis using the TEOA and PAA as reducing agent and surfactant, respectively. The size of TEOA@AgNPs-PAA (the average size of 8.65 nm) is 6 times smaller than that of the TEOA@AgNPs (52 ± 1.5 nm) without PAA. The as-prepared TEOA@AgNPs-PAA possess catalytic activity and present mimicking property of horseradish peroxidase, which are employed to fabricate colorimetric biosensors by catalyzing the reaction between H2O2 and 3,3',5,5'-tetramethylbenzidine (TMB) to produce blue oxTMB for sensitive detection of SARS-CoV-2 spiking proteins. Significantly, the small-size TEOA@AgNPs-PAA can catalyze electroreduction process of K2S2O8 to enhance the cathodic ECL signal, and their surface cap abundant TEOA molecules, which can also act as a coreactant to enhance the anodic ECL of Ru(bpy)32+. Under optimal conditions, the fabricate immunosensors for anodic and cathodic ECL determination of SARS-CoV-2 present the detection limits of 9.2 fg/mL and 14.3 fg/mL (S/N = 3), respectively. This work exhibits a promising novel strategy for the development of multifunctional AgNPs as an efficient sensing platform for the clinical diagnosis and biosensing application.

Positional encodings enable Transformers to incorporate sequential information, yet their theoretical understanding remains limited to two properties: distance attenuation and translation invariance. Because natural language lacks purely positional data, the interplay between positional and semantic information is still underexplored. We address this gap by deconstructing the attention-logit computation and providing a structured analysis of positional encodings, categorizing them into additive and multiplicative forms. The differing properties of these forms lead to distinct mechanisms for capturing positional information. To probe this difference, we design a synthetic task that explicitly requires strong integration of positional and semantic cues. As predicted, multiplicative encodings achieve a clear performance advantage on this task. Moreover, our evaluation reveals a hidden training bias: an information aggregation effect in shallow layers that we term the single-head deposit pattern. Through ablation studies and theoretical analysis, we proved that this phenomenon is inherent in multiplicative encodings. These findings deepen the understanding of positional encodings and call for further study of their training dynamics.

PURPOSE:To summarize the clinical features of group B streptococcus (GBS) meningitis in infants and identify the risk factors for poor prognosis. METHODS:The clinical data of 52 infants with GBS meningitis treated at Children's Hospital of Chongqing Medical University from January 2012 to December 2021 were retrospectively analyzed. RESULTS:A total of 48 infants (48/52, 92.3 %) presented with symptom onset at ≤90 days of age. Among 52 patients, the most prevalent clinical manifestations were fever (98.1 %), altered mental status (84.6 %) and decreased appetite (63.5 %). Subdural effusion (30/52, 57.7 %) was the most common neurological complication. One patient (1.9 %) died from cerebral herniation. Positive blood culture alone was observed in 41 cases (78.8 %), isolated cerebrospinal fluid (CSF) culture positivity in 5 (9.6 %), and dual blood-CSF culture positivity in 6 (11.5 %). The median hospital stay was 33 days. The most frequently administered antibiotic regimens were vancomycin combined with carbapenems (18/52, 34.6 %) and vancomycin plus third-generation cephalosporins (15/52, 28.8 %). Univariate analysis indicated an association between glucocorticoid use and clinical outcomes; however, multivariate analysis yielded no statistically significant variables (P < 0.05). CONCLUSIONS:GBS meningitis is most common in infants below 3 months. Both clinical manifestations and ancillary tests may be nonspecific, and definitive diagnosis relies on etiological confirmation. The risk of neurological complications is high.