Hyperandrogenism Decreases Seizure Threshold in a Rat Model of Polycystic Ovary Syndrome.

INTRODUCTION: In women of childbearing age with epilepsy, 30% experience the comorbidity of polycystic ovary syndrome (PCOS), which is marked by a higher prevalence of hyperandrogenism. Our recent clinical observations indicate the potential contribution of hyperandrogenism-induced PCOS to epilepsy susceptibility, and this study aimed to unravel the underlying factors that increase the susceptibility of females to epilepsy. METHODS: A letrozole-induced PCOS rat model was employed to simulate endogenous hyperandrogenism. The threshold of seizure was assessed through seizure kindling rates using pentetrazol and electroencephalogram recordings. Additionally, the role of androgens in epilepsy was verified through interventions using Diane-35. RESULTS: This study revealed that letrozole-induced elevated testosterone levels and PCOS-related changes in female rats. PCOS rats, through pentetrazol-kindling, exhibited a reduced seizure threshold compared with controls. Elevated testosterone levels were observed in both the hippocampal and frontal brain tissues, accompanied by changes in circulation. Two weeks of Diane-35 intervention showed a tendency to alleviate these changes, modifying testosterone levels in both the plasma and brain tissue. Western blotting and immunohistochemistry revealed increased expression of GABA-A receptor in the hippocampus and decreased AMPA receptor expression in the frontal cortex, correlating with antiepileptic status in PCOS rats. CONCLUSION: This study delves into the impact of elevated androgen levels on seizure threshold, providing crucial insights into the underpinnings of the comorbidity between PCOS and epilepsy. These findings significantly contribute to the evolving field of epilepsy research, emphasizing the imperative consideration of hormonal influences for the development of targeted therapeutic interventions in individuals with epilepsy and PCOS.

Causal link between oxidative stress and epilepsy: A two-sample Mendelian randomization study.

BACKGROUND: Although a growing body of research has indicated a strong link between oxidative stress and epilepsy, the exact nature of their interaction remains elusive. To elucidate this intricate relationship, we conducted a bidirectional Mendelian randomization (MR) analysis employing two independent datasets. METHODS: A two-sample MR analysis was performed using instrumental variables derived from genome-wide association study summary statistics of oxidative stress injury biomarkers (OSIB) and epilepsy. The OSIBs were selected from eight primary metabolic pathways associated with oxidative stress. Additionally, seven distinct epilepsy phenotypes were considered, which encompassed all epilepsy, generalized epilepsy, generalized tonic-clonic seizures, focal epilepsy, focal epilepsy with hippocampal sclerosis (focal HS), focal epilepsy with lesions other than HS (focal NHS), and lesion-negative focal epilepsy. Causal estimates were computed using the inverse-variance weighted method or the Wald ratio method, and the robustness of causality was assessed through sensitivity analyses. RESULTS: For OSIB and epilepsy, 520 and 23 genetic variants, respectively, were selectively extracted as instrumental variants. Genetically predicted higher kynurenine level was associated with a decreased risk of focal epilepsy (odds ratio [OR] 1.950, 95% CI 1.373-2.528, p = .023) and focal NHS (OR 1.276, 95% CI 1.100-1.453, p = .006). For reverse analysis, there was a suggestive effect of focal NHS on urate (OR 1.19 × 1015, 95% CI 11.19 × 1015 to 1.19 × 1015, p = .0000746) and total bilirubin (Tb) (OR 4.98, 95% CI 3.423-6.543, p = .044). In addition, genetic predisposition to focal HS was associated with higher Tb levels (OR 9.83, 95% CI 7.77-11.888, p = .034). CONCLUSION: This MR study provides compelling evidence of a robust association between oxidative stress and epilepsy, with a notable emphasis on a causal relationship between oxidative stress and focal epilepsy. Additional research is warranted to confirm the connection between oxidative stress and the risk of epilepsy and to unravel the underlying mechanisms.

The bidirectional relationship between sleep disturbance and anxiety: Sleep disturbance is a stronger predictor of anxiety.

BACKGROUND: Both sleep disturbance and anxiety are common problems that significantly affect human health, but little is known about their causal relationship. The aim of this study was to explore the causal relationship between them with a large sample of community-dwelling adults included. METHODS: Data for this study were extracted from the baseline survey of West China Natural Population Cohort Study (WCNPCS) and follow-up in the following year. The sleep quality was assessed using Pittsburgh Sleep Quality Index (PSQI), and anxiety was screened using the Generalized Anxiety Disorder Scale (GAD-7). Age, gender, educational level, marital status, smoking status, drinking status, depressive symptoms, loneliness and chronic diseases were taken as covariant factors. Logistic regression and cross-lagged models were used for data analyses. RESULTS: A total of 16699 participants (67.5 % females) were enrolled, with the average age of participants being 57.3 ± 12.7 years. A total of 40.50 % of participants experienced poor sleep quality at baseline and 40.52 % at follow-up. The prevalence of anxiety was 7.58 % at baseline and 4.62 % at follow-up. The results showed that the risk of developing anxiety in individuals with sleep disturbance at baseline was 1.89 times higher than those without (95%CI = 1.43-2.48). Similarly, anxiety increased the risk of developing sleep disturbance by 1.20-fold (95%CI = 1.03-1.39). These results were further supported by the cross-lagged panel models. CONCLUSION: Sleep disturbance and anxiety are mutually causal, and the effect of poor sleep on anxiety seems to be more significant. Timely interventions targeting sleep may help to break the vicious circle between sleep disturbance and anxiety symptoms, and improve the quality of life.

Therapeutic value of patent foramen ovale closure for drug-resistant epilepsy: A case series report.

OBJECTIVE: Closure surgery of patent foramen ovale (PFO) has been found to effectively control cryptogenic stroke and migraine, but it is uncertain whether PFO closure could also alleviate epileptic seizures. This study aims to observe the therapeutic effect of PFO closure on epileptic seizures. METHODS: Since July 11th, 2017, in the neurology department of West China Hospital, Sichuan University, Chengdu, we have been regularly monitoring patients with epilepsy who have undergone PFO closure. The patient's clinical information, such as frequency, duration, and severity of seizures, before and after surgery was recorded in detail as well as postoperative safety events. RESULTS: Of the 31 epilepsy patients who confirmed PFO observed (27 cases were drug-resistant epilepsy, 87.10%), average age of surgery was 23.74 years, and 12 cases were female (38.71%). After one-year follow-up, 26 patients (83.87%) achieved remission of seizure frequency, and 22 of whom (70.97%) experienced a remission of more than 50%. Additionally, compared to before surgery, 22 cases (70.97%) reported a decrease in the average seizure duration, and 20 cases (64.52%) reported a reduction in seizure severity. In the seizure indicators of frequency, average duration and severity, significant differences were identified between preoperative and postoperative comparisons with all test p values were <0.05. Furthermore, no serious safety events were reported except for one patient who briefly reported chest pain, and all patients expressed effective PFO closure. SIGNIFICANCE: The PFO closure has been shown for the first time to result in a significant reduction in the frequency, duration, and severity of seizures. Patients with drug-resistant epilepsy and PFO with a large shunt are ideal candidates for undergoing PFO closure. PLAIN LANGUAGE SUMMARY: Since PFO closure was found to have a good therapeutic effect on cryptogenic stroke and migraine, it has become a credible complementary therapy for the treatment of neurological diseases, and drug-resistant epilepsy with PFO is expected to become the next target disease that PFO closure could significantly improve.

Whole-cycle management of women with epilepsy of child-bearing age: ontology construction and application.

BACKGROUND: The effective management of epilepsy in women of child-bearing age necessitates a concerted effort from multidisciplinary teams. Nevertheless, there exists an inadequacy in the seamless exchange of knowledge among healthcare providers within this context. Consequently, it is imperative to enhance the availability of informatics resources and the development of decision support tools to address this issue comprehensively. MATERIALS AND METHODS: The development of the Women with Epilepsy of Child-Bearing Age Ontology (WWECA) adhered to established ontology construction principles. The ontology's scope and universal terminology were initially established by the development team and subsequently subjected to external evaluation through a rapid Delphi consensus exercise involving domain experts. Additional entities and attribute annotation data were sourced from authoritative guideline documents and specialized terminology databases within the respective field. Furthermore, the ontology has played a pivotal role in steering the creation of an online question-and-answer system, which is actively employed and assessed by a diverse group of multidisciplinary healthcare providers. RESULTS: WWECA successfully integrated a total of 609 entities encompassing various facets related to the diagnosis and medication for women of child-bearing age afflicted with epilepsy. The ontology exhibited a maximum depth of 8 within its hierarchical structure. Each of these entities featured three fundamental attributes, namely Chinese labels, definitions, and synonyms. The evaluation of WWECA involved 35 experts from 10 different hospitals across China, resulting in a favorable consensus among the experts. Furthermore, the ontology-driven online question and answer system underwent evaluation by a panel of 10 experts, including neurologists, obstetricians, and gynecologists. This evaluation yielded an average rating of 4.2, signifying a positive reception and endorsement of the system's utility and effectiveness. CONCLUSIONS: Our ontology and the associated online question and answer system hold the potential to serve as a scalable assistant for healthcare providers engaged in the management of women with epilepsy (WWE). In the future, this developmental framework has the potential for broader application in the context of long-term management of more intricate chronic health conditions.

Impacts of education level on Montreal Cognitive Assessment and saccades in community residents from Western China.

OBJECTIVES: This cross-sectional study sought to evaluate the effectiveness of the Montreal Cognitive Assessment (MoCA) and saccade in discerning the cognitive function levels among community populations characterized by diverse educational backgrounds. METHODS: Data from 665 Western China individuals encompassed MoCA scores and saccade performance. The study examined how education level and age influenced these assessments and highlighted the contrasting abilities of these measures in detecting cognitive abnormalities. RESULTS: The saccade model revealed a consistent cognitive impairment prevalence (15.5%) compared to previous clinical data (9.7% to 23.3%), while MoCA exhibited variable rates (25.1% to 52.8%). Notably, saccades and MoCA significantly diverged in detecting cognitive dysfunction. Additionally, education level had a greater impact on MoCA (effect size: 0.272) compared to saccades (0.024) affecting all MoCA sub-items, with age exerting a smaller influence on MoCA (0.037) compared to saccades (0.056). CONCLUSION: Saccades are less susceptible to the influence of education level when compared to MoCA, making saccade a potentially more suitable cognitive screening tool for rural community populations. SIGNIFICANCE: This study represents a pioneering approach by employing saccade detection within community populations to distinguish cognitive function status.

Identifying Genetic Factors of Polycystic Ovary Syndrome in Women with Epilepsy: A Whole-Genome Sequencing Study.

INTRODUCTION: Women with epilepsy (WWE) are more likely to develop reproductive endocrine disorders, especially polycystic ovary syndrome (PCOS). This study aimed to explore the genetic factors of PCOS in WWE in hope of improving individual precision diagnosis and treatment. METHODS: WWE registered at West China Hospital between January 2022 and October 2022 were enrolled in this study. Demographic and epilepsy-related characteristics were recorded, and blood samples were collected for hormones, glucose metabolism testing, and whole-genome sequencing. RESULTS: After sample sequencing, quality control, and variants selection, association analyses were performed. Pathway analysis was performed to identify involved biological pathways. The overall and PCOS "burden score" of each individual were calculated to count the deleterious variants. A total of 95 WWE were included in this study and 19 patients were diagnosed with PCOS. WWE with PCOS showed a significantly different hormone profiles and a tendency of impaired glucose metabolism. The most commonly associated genes were ZFYVE28, COL19A1, SIK3, ANKK1, PPIG, and REPIN1. The top 3 canonical pathways are adipogenesis pathway, epoxysqualene biosynthesis signaling, and glutamate degradation signaling. The most significant common variant was rs11914038 located in gene CELSR1 and rs651748 located in gene ZBTB16. In human gene connectome prioritizations, ITGA9, PNPLA2, and DAB2 are the top 3 genes having the shortest distance to known PCOS genes. CONCLUSION: Genetic factors involved in the abnormal regulation of glucose and insulin metabolism are likely to be associated with the comorbidity of PCOS in WWE. Interventions targeting these processes should be given more priority in clinical practice.

Differentiation of epilepsy and psychogenic nonepileptic events based on body fluid characteristics.

OBJECTIVE: Differential diagnosis between epileptic seizures and psychogenic nonepileptic events (PNEEs) is a worldwide problem for neurologists. The present study aims to identify important characteristics from body fluid tests and develop diagnostic models based on them. METHODS: This is a register-based observational study in patients with a diagnosis of epilepsy or PNEEs at West China Hospital of Sichuan University. Data from body fluid tests between 2009 and 2019 were used as a training set. We constructed models with a random forest approach in eight training subsets divided by sex and categories of tests, including electrolyte, blood cell, metabolism, and urine tests. Then, we collected data prospectively from patients between 2020 and 2022 to validate our models and calculated the relative importance of characteristics in robust models. Selected characteristics were finally analyzed with multiple logistic regression to establish nomograms. RESULTS: A total of 388 patients, including 218 with epilepsy and 170 with PNEEs, were studied. The AUROCs of random forest models of electrolyte and urine tests in the validation phase achieved 80.0% and 79.0%, respectively. Carbon dioxide combining power, anion gap, potassium, calcium, and chlorine in electrolyte tests and specific gravity, pH, and conductivity in urine tests were selected for the logistic regression analysis. C (ROC) of the electrolyte and urine diagnostic nomograms achieved 0.79 and 0.85, respectively. SIGNIFICANCE: The application of routine indicators of serum and urine may help in the more accurate identification of epileptic and PNEEs.

Antisaccadic eye movements in middle-aged individuals with a family history of Alzheimer's disease.

Background: Antisaccade is closely associated with cognitive ability in Alzheimer's disease (AD). However, studies regarding antisaccade in the early stages of AD are scarce. Considering that first-degree family history is a well-established risk factor for AD, we explored the influence of family history on the performance of antisaccade tasks in individuals with normal cognition. Methods: In total, 44 participants (aged 50-66 years) with a family history of AD (FH+) and 44 age-, gender-, and educational level-matched controls (FH-) were enrolled in our study. After cognitive assessment using the Montreal Cognitive Assessment and Mini-mental State Examination, participants underwent antisaccade trials, and all parameters were recorded using an eye tracker. Results: While the average velocity was relatively lower in FH+ individuals than in FH- individuals (107.9 ± 14.3°/s vs. 132.9 ± 23.7°/s, p < 0.001), FH+ individuals surprisingly showed relatively fewer uninhibited reflexive saccades (44.7 ± 26.0% vs. 56.2 ± 24.7%, p = 0.037) than the control group. They also required a relatively shorter time to detect and correct false saccades (121.6 ± 40.7 ms vs. 143.9 ± 37.0 ms, p = 0.023). Conclusions: This study showed that family history is associated with alterations in antisaccadic parameters, suggesting that eye tracking can be used to assess oculomotor control and executive function in individuals at risk of developing dementia.

Identifying risk factors for polycystic ovary syndrome in women with epilepsy: A comprehensive analysis of 248 patients.

To assess the risk factors for polycystic ovary syndrome (PCOS) in women with epilepsy (WWE) and develop a practical approach for PCOS screening based on clinical characteristic, blood indicator, and anti-seizure medication (ASM) profiles. This cross-sectional study was conducted with 248 WWE who were consecutively enrolled from the Epilepsy Center of West China Hospital between April 2021 and March 2022. The epilepsy characteristics, blood indicators, and use of ASMs were compared between WWE with and without PCOS. Multivariate logistic regression was used to identify the factors independently associated with PCOS. The differential analysis showed that younger age at onset of epilepsy (<13 years), a history of birth hypoxia, obesity (BMI ≥25 kg/m2 ), use of levetiracetam (LEV) (≥1 year), higher levels of cholesterol, luteinizing hormone (LH) and anti-Müllerian hormone (AMH), and lower levels of sex hormone-binding globulin were associated with PCOS (p < .05). Multivariate logistic regression identified that obesity (BMI ≥25 kg/m2 ), use of LEV (≥1 year), and higher levels of AMH and LH were independently associated with PCOS in WWE (p < .05). Obesity (BMI ≥25 kg/m2 ), LEV use (≥1 year), and elevated AMH and LH levels suggest an increased in the probability of occurrence of PCOS in WWE. The combination of these profiles provides a practical approach for screening PCOS in WWE.

Association Between Early Parental Death and Loneliness in Adulthood: A Community-Based Study in Southwest China.

Loneliness is a growing public health problem that threatens physical and mental health to a large extent. Compelling evidence has shown that premature parental death is strongly associated with many mental health disorders in adulthood, but whether it increases the risk of loneliness remains unclear. In this large community-based study, we included 32,682 adult participants (20-93 years old) from Southwest China and used the three-item short version of University of California, Los Angeles, Loneliness Scale to identify participants with loneliness. A total of 1,975 participants reported loneliness, which resulted in a loneliness prevalence of 6.0% in Southwest China. Logistic regression was used to evaluate the association between early parental death and loneliness after adjusting for age, gender, education level, marital status, smoking and drinking status, living status, and chronic diseases. We found that early parental death was significantly associated with loneliness [odds ratio (OR) = 1.21, 95% confidence interval (CI), 1.03-1.42]. A Sensitivity analysis excluding those with mental health disorders (796 participants) yielded similar results (OR = 1.26, 95% CI = 1.06-1.49). We also found that being younger, single, divorced, or widowed, and more educated; living alone; and having chronic disorders were associated with loneliness. We conclude that childhood parental death is associated with loneliness in adulthood, suggesting the need for early intervention in affected children to prevent long-term adverse neuropsychiatric effects.

Association between patent foramen ovale and migraine without aura: a community-based cross-sectional study in China.

OBJECTIVES: To assess the influence of patent foramen ovale (PFO) on the prevalence of migraine without aura based on propensity score-matched samples in Southwest China. DESIGN: Propensity-matched cross-sectional study. PARTICIPANTS: Residents over 20 years of age were recruited from 15 communities of Western China from July 2020 to October 2020. A total of 3741 residents having accepted to undergo contrast-transthoracic echocardiography and a standard structured questionnaire was assessed for the relationship between PFO and migraine without aura. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measures were the prevalence of migraine without aura across different degrees of right-left shunts. RESULTS: A total of 3741 participants were included. Among them, 881 participants were diagnosed with PFO. The prevalence of migraine without aura in the PFO group was 12.83%, significantly higher than the other group (7.83%, p<0.0001). Analyses of the matched samples showed that the presence of a PFO increased the morbidity risk of migraine without aura (p < 0.001; OR=1.71, 95% CI 1.19 to 2.47). CONCLUSION: This community-based cross-sectional study pointed to a strong association between PFO and migraine without aura, especially when the shunt is large. TRIAL REGISTRATION NUMBER: ChiCTR1900024623.

Metabolomics Provides Novel Insights into Epilepsy Diagnosis and Treatment: A Review.

Epilepsy is one of the most common diseases of the central nervous system. The diagnosis of epilepsy mainly depends on electroencephalograms and symptomatology, while diagnostic biofluid markers are still lacking. In addition, approximately 30% of patients with epilepsy (PWE) show a poor response to the currently available anti-seizure medicines. An increasing number of studies have reported alterations in the blood, brain tissue, cerebrospinal fluid and urine metabolome in PWE and animal models of epilepsy. The aim of this review was to identify potential metabolic biomarkers and pathways that might facilitate diagnostic, therapeutic and prognostic determination in PWE and the understanding of the pathogenesis of the disease. The PubMed and Embase databases were searched for metabolomic studies of PWE and epileptic models published before December 2020. The study objectives, types of models and reported differentially altered metabolites were examined and compared. Pathway analyses were performed using MetaboAnalyst 5.0 online software. Thirty-five studies were included in this review. Metabolites such as glutamate, lactate and citrate were disturbed in both PWE and epileptic models, which might be potential biomarkers of epilepsy. Metabolic pathways including alanine, aspartate and glutamate metabolism; glycine, serine and threonine metabolism; glycerophospholipid metabolism; glyoxylate and dicarboxylate metabolism; and arginine and proline metabolism were involved in epilepsy. These pathways might play important roles in the pathogenesis of the disease. This review summarizes metabolites and metabolic pathways related to epilepsy and provides a novel perspective for the identification of potential biomarkers and therapeutic targets for epilepsy.

Gastric Electrical Dysarrhythmia in Probable Rapid Eye Movement Sleep Behavior Disorder.

Background: Subjective gastrointestinal complaints have been repeatedly reported in patients with REM sleep behavior disorder (RBD), but objective evidence is scarce. We aimed to objectively investigate the gastrointestinal dysfunction in individuals with probable RBD (pRBD) using an electrogastrogram. Methods: Thirty-two participants with pRBD and 60 age- and gender-matched healthy controls were enrolled. pRBD was diagnosed based on questionnaires and further assessed by experienced neurologists. After thorough assessment of participants' subjective gastrointestinal symptoms, preprandial and postprandial gastric activities were measured using an electrogastrogram. Dominant frequency, dominant power ratio, and the ratio of preprandial to postprandial power were analyzed. Results: Among the gastric symptoms, hiccup (34.8 vs. 9.6%, p = 0.017) and postprandial gastric discomfort (43.5 vs. 15.4%, p = 0.017) were more frequent in participants with pRBD than in controls. The dominant frequency on the electrode overlying the gastric pyloric antrum was lower in pRBD than in healthy controls (2.9 [2.6-2.9] vs. 2.9 [2.9-3.2] cpm, p = 0.006). A reduced dominant power ratio from the same electrode was also found in individuals with pRBD (60.7 [58.0-64.5] vs. 64.2 [58.7-69.6] %, p = 0.046). Conclusion: Patients with pRBD have a higher rate of gastric dysfunction, which presented as irregular slow wave rhythmicity on an electrogastrogram.

Behavioral and Brain Structural Changes in Kindled Rats Induced by Coriaria Lactone/Pentylenetetrazol.

Epilepsy is a common chronic neurological disease that is characterized by spontaneous seizures. It is commonly comorbid with behavioral and mood disorders. No studies have yet examined the behavioral or structural brain changes associated with coriaria lactone (CL)-induced and pentylenetetrazol (PTZ)-induced kindlings. This study examined whether the increased seizure susceptibility induced by CL/PTZ is accompanied by behavioral impairments and aimed to identify associated structural brain changes. Kindling models were induced using CL and PTZ, with 10 rats in each group. After successful kindling, rats were subjected to brain structural imaging using T2-weighted imaging and underwent behavioral tests, namely, the open field test, water maze tasks, and contextual fear conditioning. Voxel-based morphometry was then used to identify possible brain structural changes associated with kindling and/or behaviors. Support-vector machine learning was also applied for the integrative analysis of behavioral changes and structural brain imaging. In the open field test, both the CL (P = 0.04) and PTZ groups (P = 0.002) spent more time in the central area than the control group. Only the PTZ group (50.29 ± 29.56 s) showed a freezing time that was significantly less than that of the control group (94.8 ± 41.04 s; P = 0.024, Tukey's HSD-corrected) in contextual fear conditioning, which is suggestive of impaired fear-associated learning ability. Furthermore, brain imaging analysis revealed that the gray matter volume (GMV) of the hippocampus changed in both the CL and PTZ groups when compared to control. The support-vector machine learning model indicated that the retrosplenial dysgranular and primary somatosensory cortices were associated with both of the mentioned kindling models. Furthermore, the support-vector regression model results indicated that kindling-associated GMV changes can be used to predict general exploratory activity in the open field test. In conclusion, this is the first study to report greater general exploratory activity in a CL-induced kindling model. Moreover, the general exploratory activity in the open field test can be predicted by the GMV of brain regions associated with kindling.

Time-Dependent Impairment of Fear Conditioning and Associated Brain Regions After Pilocarpine-Induced Status Epilepticus.

Our study aimed to demonstrate time-dependent declarative memory changes and its associated brain regions after status epilepticus (SE) using structural imaging techniques and machine learning methods. Pilocarpine was administrated to establish the SE model. At four different time points after SE (1, 2, 3, and 4 months, respectively), rats were subjected to structural imaging acquisition as well as contextual fear conditioning for the measurement of brain structural changes and declarative memory. Voxel-based morphometry (VBM) analysis were performed. Those significantly different regions were selected as features for training support vector machine (SVM). A linear kernel was chosen for regression of declarative memory. Leave-one-out cross-validation was applied to ensure generalization. Our results showed that the pilocarpine groups displayed the most severely impaired declarative memory at 2 months after SE and improved afterward, but failed to recover to the normal condition at 4 months after SE. The pilocarpine groups showed lower gray matter volumes and larger cerebrospinal fluid (CSF) volumes. After controlling for the total brain volumes, ANOVA demonstrated gray matter volume changes in the CA1 subfield of the hippocampus, primary somatosensory cortex, entorhinal cortex, etc. The combination of VBM and SVM identifies the somatosensory cortex and entorhinal cortex as the correlated brain regions for declarative memory dysfunctions after SE. Our study indicates that compensational mechanisms might be triggered to help with the recovery of memory functions after SE. Structural changes of the somatosensory cortex and entorhinal cortex might be involved in memory impairment after SE.

Integrative analysis of non-targeted lipidomic data and brain structural imaging identifies phosphatidylethanolamine associated with epileptogenesis.

INTRODUCTION: Epilepsy is a chronic disease, while epileptogenesis is a latent period where brain will be transformed into an epileptic one. Mechanisms of epileptogenesis remain unclear. OBJECTIVES: We aim to provide information of hippocampal lipidomic changes related with epileptogenesis in two kindling models. Combining hippocampal structural imaging indices, our study also attempts to assess biochemical alterations as a function of epileptogenesis in a non-invasive way. METHODS: We constructed two kinds of chemical kindling models, which have long been used as models of epileptogenesis. Two kindling and one control groups were all subjected to structural imaging acquisition after successfully kindled. Voxel-based morphometry, a postprocessing method for brain imaging data, was used to segment and extract hippocampal gray matter volume for subsequent integrative analysis. LC-MS based lipidomic analysis was applied to identify distinct hippocampal lipidomic profiles between kindling and control groups. Further, we regress hippocampal structural indices on lipids to identify those associated with both epileptogenesis and brain structural changes. RESULTS: We report distinct lipidomic profiles between kindling groups and control. A total of 638 lipids were detected in all three groups. Among them were 98 individual lipids, showing significant alterations, in particular lipid class of phosphatidylethanolamine (PE), glucosylceramide and phosphatidylcholine. Hippocampal gray matter volumes were found significant different between groups (P = 0.0223). After combining brain imaging data, we demonstrate several individual PE, namely PE(O-18:1_22:3), PE(O-18:1_22:6) and PE(18:1_18:1), are associated with both epileptogenesis and hippocampal gray matter volume. CONCLUSION: This study suggests metabolic pathway of PE might involve in epileptogenesis. Also, for the first time, we link level of PE with structural brain imaging indices, in an attempt to potentiate the futuristic application of noninvasive brain imaging techniques to identify epileptogenesis in its latent period.

Antiepileptic drugs for acute encephalitic patients presented with seizure.

OBJECTIVE: The aim of this study was to clarify the pattern and efficacy of antiepileptic drugs (AEDs) in acute encephalitis and discuss how long AEDs should be used after the acute phase. METHODS: Patients with acute encephalitis who presented with seizure were enrolled. The clinical features were systematically gathered, and the information about AEDs and seizures was obtained by a clinical follow-up and (or) a telephone interview based on a structured form. RESULTS: A total of 327 patients were enrolled, and the mean follow-up period was 63.8 (14-123) months. The risk of seizure relapse was estimated as 43.6% five years after the acute phase and the first three months was the peak time for relapse. Univariate analysis showed that status epilepticus, more than one seizure, cerebral spinal fluid protein level, abnormal MRI finding, temporal lobe involvement, and epileptiform discharge were related to seizure relapse. But only more than one seizure (OR = 2.80 (95% CI 1.29-6.09), p = 0.009) and temporal lobe involvement (5.34 (2.68-10.64), p < 0.001) remain predictive on multivariate regression analysis. For patients with only one seizure and no temporal lobe involvement, the risk of seizure relapse was similar between those with or without AED (2/29 vs. 4/28, p = 0.423). For the rest, the risks of relapse were similar among those who took sodium valproate and levetiracetam. SIGNIFICANCE: For patients with only one seizure and no temporal lobe involvement, AEDs may not be strictly needed. The first three months after acute phase was the peak time for relapse and AEDs may should be used during this period. Both sodium valproate and levetiracetam could be selected.

Predictors of drug-resistance in epilepsy with auditory features.

OBJECTIVE: To investigate predictors of drug-resistance in epilepsy with auditory features (EAF). METHODS: Drug-resistant epilepsy (DRE) was defined according to International League Against Epilepsy guidelines. For univariate analysis, the chi-squared, Fisher's exact, and Mann-Whitney test were used. Odds ratios (OR) and 95% confidence intervals (CIs) of predictors were estimated by logistic regression analyses. RESULTS: A total of 107 patients (52 male) between the ages of 13.0 and 78.8 years were included in this cohort. In univariate analysis, ten variables, including age at seizure onset < or = 10 years, febrile seizures, psychiatric disorders, seizures during sleep, multiple first ictal symptoms, electroencephalogram epileptiform discharges during waking, non-specific abnormalities in electroencephalogram, oxcarbazepine as the first drug, oxcarbazepine in the first two drugs and valproic acid in the first two drugs, showed possibilities as prognostic factors of EAF (p < 0.10). After logistic regression analyses, two positive predictors of drug-resistance, including age at seizures onset < or = 10 (OR = 6.37, 95% CI = 1.08-37.7, p = 0.041) and seizures during sleep (OR = 4.42, 95% CI = 1.45-13.48, p = 0.009) were found. Oxcarbazepine as the first AED is a negative predictive factor of drug-resistance (OR = 0.22, 95% CI = 0.06-0.84, p = 0.027). CONCLUSIONS: Three predictors may help early diagnosis of DRE in EAF. Early use of oxcarbazepine is a negative predictor of drug-resistance, which may provide an intervention point to minimize the risk of drug-resistance.

Plasma luteinizing hormone level affects the brain activity of patients with polycystic ovary syndrome.

OBJECTIVE: Cognitive function has been reported to be impaired in women with polycystic ovary syndrome (PCOS). This study aimed to investigate the effect of PCOS on brain activity and explore the relationship between brain activity and sex hormone levels in women with PCOS (WPCOS). METHODS: Twenty-one women aged 18-45 years old with new-diagnosed PCOS were enrolled. Plasma levels of six sex hormones including luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were tested during the 2-5 days of their menstrual periods. Twenty-seven healthy controls (HC) were recruited. Every subject underwent a resting-state functional magnetic resonance imaging (fMRI). The amplitude of low-frequency fluctuation (ALFF) of the whole brain was evaluated followed by the functional connectivity (FC) analysis. Finally, the correlation between the ALFF, FC of the significant areas and the plasma hormone levels were analyzed. RESULTS: The patients showed increased ALFF value in the left inferior temporal gyrus (ITG.L) and decreased ALFF value in the left inferior occipital gyrus (IOG.L) as well as the superior frontal gyrus (SFG.R, P < 0.005). For the FC analysis, patients showed decreased FC in SFG.R with the right middle frontal gyrus (MFG.R, P < 0.05). The FC between SFG.R and MFG.R was negatively correlated with LH level (R=-0.594, P = 0.005) and with the LH/FSH ratio (R=-0.521, P = 0.015). CONCLUSION: PCOS can induce changes in activities of brain regions responsible for visuospatial working memory, face processing and episodic memory. The reduced functional connectivity within the right frontal lobe is related with the high LH level in WPCOS.