Jiajia Fang

Background: Insulin-like growth factor 1 (IGF-1) has neurotrophic and neuroprotective properties, but its relationship with epilepsy risk and cognitive outcomes remains unclear. We investigated whether serum IGF-1 was associated with incident epilepsy and cognitive performance in a large population-based cohort. Methods: We performed a prospective analysis of the UK Biobank including 466,857 participants with baseline serum IGF-1 measurements. Incident epilepsy was identified from hospital records and self-report. Associations with epilepsy risk were assessed using prespecified Cox proportional hazards models, restricted cubic splines, and sensitivity analyses. Cross-sectional and longitudinal analyses were used to examine cognitive outcomes. Results: Over more than 15 years of follow-up, 4,532 participants developed incident epilepsy. Higher serum IGF-1 was consistently associated with a lower risk of incident epilepsy; in the primary model, each 1 nmol/L increase was associated with a lower hazard of incident epilepsy (HR = 0.978, 95% CI 0.973–0.984). The association was nonlinear and L-shaped, with a steeper increase in risk at lower IGF-1 concentrations and an apparent plateau above approximately 20 nmol/L. Per-standard-deviation, quartile-based, lagged, and alcohol-frequency sensitivity analyses showed similar results. In cross-sectional analyses of participants with epilepsy at baseline, higher IGF-1 was nominally associated with faster reaction time and better prospective memory, but neither association remained significant after false discovery rate correction. Exploratory longitudinal analyses in the epilepsy subgroup were limited by sample size and did not show significant cross-lagged associations. In the full cohort, higher baseline IGF-1 was associated with better subsequent performance in several cognitive domains, although these findings were not epilepsy-specific. Conclusions: Lower serum IGF-1 was independently associated with a higher risk of incident epilepsy in this large population-based cohort. Evidence for cognitive associations was more limited, with only nominal cross-sectional findings in baseline epilepsy and exploratory, non-epilepsy-specific longitudinal signals. These results support further investigation of circulating IGF-1 as a candidate biomarker and biologically relevant pathway rather than as evidence of a causal or therapeutic target.

Background: Ischemic stroke is a leading cause of death and disability worldwide, yet the systemic metabolic mechanisms underlying poor functional recovery remain incompletely understood. Dysregulated lipid metabolism is a key pathogenic factor, and advances in metabolomics and lipidomics provide new opportunities for discovering pathophysiological signatures. Methods: In this exploratory study, we integrated serum metabolomic and lipidomic profiling in 44 patients with acute ischemic stroke, stratified by favorable ( n = 23) or unfavorable ( n = 21) 90-day functional outcomes. Differential metabolites and lipids were identified, pathway-related molecular alterations were characterized, and candidate markers were evaluated to establish a proof-of-concept metabolic signature. Results: Patients with unfavorable outcomes exhibited global metabolic reprogramming characterized by structural lipid disassembly (widespread reductions in membrane phospholipids, including phosphatidylcholines and ether phospholipids), mitochondrial energy failure (acylcarnitine abnormalities consistent with impaired β -oxidation), and antioxidant depletion (marked by decreased cis-caffeic acid). An exploratory three-marker panel—the C8:2-OH(3)/C18:2-OH(3) ratio, the free DHA/PC(44:12) ratio, and cis-caffeic acid—showed promising discriminatory potential in this derivation cohort (AUC = 0.950). Adding this metabolic panel to the initial NIHSS score improved the AUC to 0.975, suggesting incremental value beyond clinical assessment alone. Conclusion: Integrated serum metabolomics and lipidomics identified a metabolic signature reflecting lipotoxicity, mitochondrial dysfunction, and oxidative stress. These preliminary findings highlight systemic metabolic reprogramming as a potential driver of unfavorable outcome and provide a proof-of-concept for combining molecular phenotyping with conventional clinical scales. Without external validation and multiple-testing correction, these results should be viewed as hypothesis-generating.

Objective: Folic acid (FA) is essential for fetal development, while the benefits and optimal dose in pregnant women with epilepsy (PWWE) remain unclear. This study explores effects of FA supplementation, dose, and initiation time on offspring outcomes in PWWE. Methods: This multi‐center cohort recruited PWWE from 58 hospitals in China. Anti‐seizure medication (ASM) and FA exposures were categorized by first‐trimester use. The primary outcome was a composite of preterm birth, low birth weight (LBW), major congenital anomalies (MCAs), fetal death, and neurodevelopmental delay. Logistic regression models assessed the associations between FA exposure, dose, initiation time, and adverse outcomes, adjusting for demographics and epilepsy characteristics, with stratification by maternal ASM use. Dose–response relationships were analyzed using restricted cubic splines. Results: Among 1013 women with 1209 pregnancies, 952 received FA. In ASM‐exposed pregnancies, FA supplementation was associated with lower risks of composite adverse offspring outcomes (adjusted odds ratio [aOR] .59, 95% confidence interval [CI] .387–.911) and fetal death (aOR .127, 95% CI .054–.296), whereas no significant differences were observed between preconception and first‐trimester initiation. Compared to no supplement, supplementation with .4 mg/day protected against fetal death (aOR .185, 95% CI .078–.428); doses exceeding .4 mg/day further reduced risk of composite adverse outcomes (aOR .343, 95% CI .162–.675), and doses above 1 mg additionally showed trends toward decreased preterm birth in ASM‐exposed pregnancies (aOR .338, 95% CI .104–.943). Compared with .4 mg supplementation, doses above 1 mg/day were associated with a lower risk of LBW (aOR .208, 95% CI .05–.58). Significance: FA supplementation was associated with lower risks of composite adverse offspring outcomes in ASM‐exposed pregnancies, specifically at doses exceeding .4 mg. No such associations were observed in pregnancies not exposed to ASMs. However, the optimal upper limit of high‐dose FA supplementation requires further investigation.

Objective: Temporal Lobe Epilepsy (TLE) often leads to cognitive decline. The Basal Forebrain Cholinergic System (BFCS), essential for memory processes, may play a critical role. This study investigates BFCS alterations, associated white matter tracts, and cognitive correlations in TLE patients. Methods: We analyzed 100 unilateral TLE patients and 25 healthy controls. Neuropsychological assessments included the Wechsler Memory Scale‐Revised and the Rey Complex Figure Test. Regions of interest (ROIs), such as the hippocampus, amygdala, and dorsolateral prefrontal cortex, were identified using the AAL3 atlas and SPM 8 Anatomy toolbox. BFCS tract integrity was assessed using FSL probabilistic tractography, focusing on FA and MD values. Results: Both left TLE (LTLE) and right TLE (RTLE) groups displayed significant deficits in memory quotient, verbal/nonverbal memory, and visuospatial working memory, with hippocampal sclerosis (HS) patients showing greater impairment. LTLE patients exhibited extensive BFCS impairment versus controls, with reduced FA (bilateral hippocampus/amygdala, all p < 0.01) and elevated MD (bilateral hippocampus p < 0.05; bilateral amygdala p < 0.01; DLPFC p < 0.05). RTLE showed localized damage: decreased FA (left hippocampus/right amygdala, both p < 0.05) and increased DLPFC MD ( p < 0.05). HS intensified BFCS‐right hippocampal and bilateral amygdala damage in TLE. Correlation analyses indicated positive associations between BFCS‐right hippocampal FA and verbal and nonverbal memory, whereas its MD negatively correlated with nonverbal memory decline. BFCS‐right amygdala FA correlated with both memory domains, and BFCS‐DLPFC MD inversely correlated with memory quotient. Elevated MD in the right Ch4 to ipsilateral hippocampal tracts served as a sensitive imaging biomarker for nonverbal memory impairment. Conclusion: TLE patients exhibit cognitive and visual‐spatial memory deficits, with BFCS tract damage being more pronounced in LTLE and HS patients. The BFCS and its projection fibers demonstrate potential correlations with cognitive function and may be involved in the neural mechanisms of cognitive impairment in TLE.

Introduction Patients with epilepsy (PWE) face an elevated risk of osteoporosis and bone fractures. This study aims to elucidate bone metabolic alterations in PWE and identify early detection biomarkers and contributing factors. Methods This cross-sectional study analyzed PWE from the Epilepsy Clinical database stratified by anti seizure medication (ASM) exposure duration. We analyzed bone turnover markers (BTMs), including 25-hydroxy vitamin D, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), β-crosslaps (β-CTX) and β-CTX/OC ratio. The effects of epilepsy and ASMs on bone metabolism were analyzed by XGBoost model and SHapley Additive exPlanations (SHAP). Finally, we analyzed the mediation analyses assessing inflammatory pathway contributions. Results A total of 476 PWE were included in this study. Compared to ASM-naïve PWE, those receiving > 2 years of ASM therapy exhibited a reduced β-CTX/OC ratio (p = 0.002), while P1NP levels declined only after > 10 years of treatment (p < 0.001). Longitudinal data revealed a continued annual decline in the β-CTX/OC ratio during the 2-year follow-up period. After adjusting for confounders, longer ASM exposure duration was significantly correlated with decreased P1NP, β-CTX and β-CTX/OC ratio levels (β = − 1.74, 95% CI − 2.56 to − 0.92; p < 0.001). XGBoost-SHAP analysis identified valproic acid (VPA), oxcarbazepine (OXC) and history of status epilepticus as key contributors to β-CTX/OC ratio variability. Polytherapy had a more pronounced effect than monotherapy, particularly when levetiracetam was combined with VPA or OXC. Mediation analysis demonstrated that platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio mediate epilepsy/ASM-related bone metabolic alterations. Conclusion PWE exhibit dynamic bone metabolic alterations. Following > 2 years of ASM therapy, osteoclast inhibition precedes the onset of osteoblast dysfunction. Prolonged ASM exposure eventually reduces bone formation markers, indicating progressive impairment of osteoblastic function and a concomitant decline in bone-forming capacity. Consequently, the β-CTX/OC ratio represents a pivotal early biomarker for monitoring bone health deterioration, demonstrating significant clinical utility.

Objective: The potential impact of antiseizure medications (ASMs) on abortion rate and bone metabolism in the offspring of pregnant women with epilepsy (WWE) is currently unknown. This research aimed to assess the potential risk by conducting a comparative analysis of bone metabolism‐related indicators in the offspring of WWE.Methods: We retrospectively analyzed data from 83 epileptic parturients receiving antenatal care at our hospital and a co‐operative hospital from January 1, 2012, to December 31, 2021, comparing them to a control group of 249 parturients. The study analyzed and compared the two groups' growth parameters, including delivery mode, femoral length, biparietal diameter, and birth weight. Differences in femoral length, biparietal diameter, and birth weight among different ASM groups were also examined.Results: WWE were more likely to undergo a cesarean section with a lower abortion rate (55.4% vs. 37.3%, P = 0.004). After adjusting for potential confounding variables, offspring femoral length in WWE was significantly reduced compared to the control group (6.812 cm vs. 6.923 cm, P < 0.0001). Moreover, those born to WWE using multiple ASMs had significantly reduced femoral and biparietal lengths compared to those whose mothers used a single ASM or none (P < 0.0001). Additionally, birth weight was significantly lower in offspring of WWE using multiple ASMs than those not using ASM (P < 0.05).Interpretation: WWE experienced fewer abortions but worse negative offspring outcomes. The bone metabolism of the offspring of WWE was decreased and exhibited shortened femoral length, particularly in those on multiple ASMs.

Epilepsy is a prevalent chronic neurological disorder that can significantly impact patients’ lives. The incidence and risk of psychosis in individuals with epilepsy are notably higher than in the general population, adversely affecting both the management and rehabilitation of epilepsy and further diminishing patients’ quality of life. This review provides an overview of the classification and clinical features of psychosis of epilepsy, with the aim of offering insights and references for the clinical diagnosis and treatment of various types of psychosis of epilepsy. Additionally, we examine the potential pathophysiological mechanisms underlying the psychosis of epilepsy from three perspectives: neuroimaging, neurobiology, and genetics. The alterations in brain structure and function, neurotransmitters, neuroinflammatory mediators, and genetic factors discussed in this review may offer insights into the onset and progression of psychotic symptoms in epilepsy patients and are anticipated to inform the identification of novel therapeutic targets in the future.

Glutamic acid decarboxylase 65 (GAD65) antibody-associated epilepsy and diplopia are relatively rare. This article retrospectively analyzed the disease development, diagnosis and treatment process of two cases of GAD65-associated epilepsy with diplopia. Both patients initially exhibited seizures, followed by the onset of diplopia and nystagmus. Due to differences in their diagnostic processes, the two patients showed varying prognoses after treatment. When diplopia and nystagmus are present in patients with epilepsy, these symptoms are often easily attributed to the side effects of antiepileptic medications or not associated with the epilepsy, potentially leading to the oversight of the possibility of GAD65 neurological syndrome. Therefore, clinicians should be aware of the potential association of anti-GAD65 antibodies in epilepsy patients presenting with diplopia, avoidance of missed diagnosis. Furthermore, diplopia and nystagmus may be precursors to ataxia, therefore, when diplopia occurs, proactive treatment should be initiated to prevent disease progression and avoid poor patient outcomes.