Protective effects of isoquercitrin on streptozotocin-induced neurotoxicity.

Alzheimer's disease (AD) is characterized by irreversible and progressive memory loss and has no effective treatment. Recently, many small molecule nature products have been identified with neuroprotective functions and shown beneficial effects to AD patients. In the current study, we thus performed a small scale screening to determine the protective effects of natural compounds on streptozotocin (STZ)-induced neurotoxicity and Alzheimer's disease (AD). We found that a lead flavonoid compound, isoquercitrin (ISO) display the most effective anti-cytotoxic activities via inhibiting STZ-induced apoptosis, mitochondria dysfunction and oxidative stress. Treatment with ISO largely rescues STZ-induced differentiation inhibition and enhances neurite outgrowth of Neuro2a (N2a) cells in vitro. Moreover, oral administration of ISO protects hippocampal neurons from STZ-induced neurotoxicity and significantly improves the cognitive and behavioural impairment in STZ-induced AD rats. In general, our screening identifies ISO as an effective therapeutic candidate against STZ-induced neurotoxicity and AD-like changes.

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.

Do premature and postterm birth increase the risk of epilepsy? An updated meta-analysis.

BACKGROUND: Many studies have reported that premature birth is associated with a higher incidence of epilepsy, and postterm birth also increases the risk of epilepsy. The effects of different gestational ages (GAs) on epilepsy have become a research hotspot, but the findings of these studies remain controversial, and no systematic review has been performed until now. OBJECTIVE: The aim of this study was to evaluate the impact of different GAs on the incidence of epilepsy. DATA SOURCES: The main databases, including PubMed, Medline, Embase, Cochrane Library, and Web of Science, were searched using the terms "preterm/premature/early/postterm/postmature/late/delayed delivery/birth", "gestational age", and "epilepsy/seizure" for eligible studies published up to April 1, 2019. The search was limited to English-language articles. STUDY SELECTION: Observational studies investigating the association between epilepsy and premature or postterm birth were included in this meta-analysis. We only selected studies that had clearly reported GA and the occurrence of epilepsy. DATA EXTRACTION AND ANALYSIS: Two reviewers independently extracted the data. The quality of the included studies was examined in accordance with the Newcastle-Ottawa criteria, and the heterogeneity and publication bias were tested. We used sensitivity and subgroup analyses to determine the source of heterogeneity. A logistic randomized-effects model was used to assess the collected data when I2 ≥ 50%. MAIN OUTCOMES: The primary outcome was the odds ratio (OR) of epilepsy. RESULTS: The research included eleven eligible studies with a total of 4,513,577 participants. Studies involving premature birth showed that the risk of epilepsy was 2.16 times higher in the premature birth group (<37 weeks) than in the full-term birth group (≥37 weeks) (OR [99% confidence interval [CI]] = 2.16 [1.80, 2.58]; P < 0.001). Those born before 32 weeks were associated with an increased occurrence of epilepsy when compared with those born at 32-36 weeks (OR [99% CI] = 2.73 [1.90, 3.94]; P < 0.001). However, the difference in the incidence of epilepsy between postterm children (41 weeks or more) and full-term children (37-40 weeks) was not statistically significant (OR [99% CI] = 1.05 [0.98, 1.12]; P = 0.067). CONCLUSIONS: Preterm birth was closely associated with a higher risk of epilepsy throughout childhood that persisted into adulthood, and the association became stronger as GA decreased, while there was no significant difference in the risk of developing epilepsy between postterm and full-term offspring.

cAMP response element-binding protein and Yes-associated protein form a feedback loop that promotes neurite outgrowth.

The cAMP response element-binding (CREB) protein is a member of the CREB/activating transcription factor family that is activated by various extracellular stimuli. It has been shown that CREB-dependent transcription stimulation plays a key role in neuronal differentiation and plasticity, but the underlying mechanisms remain largely elusive. Here, we show that Yes-associated protein (YAP) is a direct target induced by CREB upon retinoic acid (RA)-induced neurite outgrowth stimuli in N2a cells. Interestingly, YAP knockout using the CRISPR/Cas9 system inhibits neuronal differentiation and reduced neurite length. We further show that YAP could directly bind to CREB via its N-terminal region, and loss of YAP results in instability of phosphorylated CREB upon neurite outgrowth stimuli. Transient expression of YAP could largely restore CREB expression and neurite outgrowth in YAP knockout cells. Together, our results suggest that CREB and YAP form a positive feedback loop that is critical to maintain the stability of phosphorylated CREB and promote neurite outgrowth.

Pregnancy outcome in women with epilepsy in Western China: A prospective hospital based study.

OBJECTIVE: Gaps exist in the diagnosis and treatment of women with epilepsy (WWE) between China and Euro-American countries. We aim to find out and share our experience of the multidisciplinary integrated treatment for WWE. METHODS: We prospectively registered WWE who were diagnosed by both epileptologists and obstetrician in our green way system for the past 5years (2009-2015). Registration information include years of education, epilepsy history, seizure type and frequency, pregnancy and delivery complications, delivery mode, and Apgar score of newborn. All data were analyzed by SAS 9.3 version. RESULTS: We included 137 cases of maternal epilepsy (155 pregnancies with average maternal age of 26years old). 18 cases underwent epilepsy surgery before pregnancy. 103 pregnancies (66.45%) were cesarean section, 52 (33.55%) were natural childbirth, only 10 pregnancies have pregnancy complications, 2 have delivery complication, and 15 have seizures during delivery process. Most offspring were healthy when they were born (only 11 newborn got Apgar score<7). For drug treatment, patients never took AEDs or withdrew AEDs in 55 (35.48%) pregnancies. For folic acid supplementation, only 9 (5.81%) achieved the dose recommended by ILAE guideline (5mg/day). For the seizure frequency, 108 pregnancies (69.68%) did not changed, 3 (1.94%) reduced, 44(28.39%) increased and mainly increased in the first and last trimesters. For feeding way, 90 (58.06%) chose artificial feeding, followed by 39 (16.77%) of mixed feeding and 26 of breastfeeding. CONCLUSION: Clinical features and perinatal outcome of Chinese WWE are similar to western WWE. For mode of delivery, even suggested by our epileptologists and obstetrician to deliver naturally, more patients selected cesarean section. Moreover, withdrawal of AEDs during pregnancy is common. Therefore, it is necessary to pay more attention to standard management of WWE and establish a more practical green way for WWE in China, to keep up with developed countries and improve the health level of birth in China.

The impact of childhood parental loss on risk for depression and anxiety in adulthood: A community-based study in Southwest China.

PURPOSE: Lack of parental raising is an important reason for parental loss in China due to urbanization. We aimed to explore the association between parental loss (including parental death, divorce, alcoholism, crime, drug addiction, bedridden, and lack of parental raising) before 17 years old and mental health disorders in adulthood in Southwest China. METHODS: Childhood parental loss, age, gender, socioeconomic status, smoking, drinking, and medical history were self-reported. Patient Health Questionnaire 9 (PHQ-9) and Generalized Anxiety Disorder 7 (GAD-7) were used for identifying depression and anxiety, respectively. We use logistic regression with inverse probability weighting according to the propensity score to assess the risk of childhood parental loss on mental health disorders in adulthood. RESULTS: A total of 8014 adults were enrolled in this study. Childhood parental loss increased the risk of adulthood depression (OR, 1.60, 95%CI, 1.30-1.98) but not anxiety (p= 0.07) after adjustment of all covariates. Sensitivity analyses including logistic regression with original data, nearest neighbor matching, full matching, and propensity score as the only covariate all yielded similar results. LIMITATIONS: Recall bias could not be fully eliminated due to the retrospective nature of study design. Our study had been conducted in a less-prosperous area in Southwest China and the results may not be representative at nation level. CONCLUSIONS: Childhood parental loss was associated with depression in adulthood in Southwest China, highlighting the need for early intervention in children with parental loss, to prevent long-term negative effects on their mental health.

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.

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.

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.

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.

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.

Trends in epilepsy diagnosis and surgery in western China during 2009-2017.

OBJECTIVE: Despite the strong evidence for the efficacy of surgery to treat temporal lobe epilepsy, the number of such surgeries has plateaued in western countries. This study examined trends in the number of epilepsy cases diagnosed, number of surgeries performed, and certain characteristics of surgery patients in western China between January 2009 and December 2017. METHODS: Data were obtained for a population-based sample from a healthcare information system, as well as for a patient population from West China Hospital. Age at epilepsy onset, age at surgery, duration of epilepsy, and type of epilepsy pathology based on surgical samples were analyzed. RESULTS: Data were obtained for 14,710 hospitalizations from the healthcare system and 17,302 hospitalizations from West China Hospital. The number of hospitalizations, but not the number of epilepsy surgeries, increased during the study period. Patients' age at epilepsy onset, age at surgery or epilepsy duration did not change significantly during the study period. SIGNIFICANCE: Our analysis suggests that in western China, as in western countries, the number of temporal epilepsy surgeries has plateaued. In contrast, disease-modifying factors have not changed over time in western China. Further studies are needed to explore what may contribute to these findings.

Decision-making in patient s with epilepsy: A systematic review and meta-analysis.

OBJECTIVE: Decision-making (DM) is an essential ability in everyday life. Some studies have reported DM deficits in patients with epilepsy. However, the reliability of the conclusions was limited by small sample sizes and inconsistent results. This review evaluated the current evidence concerning DM ability in epilepsy to provide a more detailed understanding and reliable conclusions. METHODS: Seven databases were searched to collect studies about DM ability in epilepsy. The weighted mean difference (WMD), standardised mean difference (SMD) and 95% confidence interval (CI) were used to compare continuous variables. RESULTS: A total of 13 studies, including 395 patients with epilepsy, met our inclusion criteria. The overall size of DM deficits was moderate (SMD = -0.372, 95% CI = -0.529 - -0.215, p < 0.001). The performance of the Iowa Gambling Task were impaired (WMD = -11.961, 95% CI = -20.543 - -3.380, p = 0.006; SMD = -0.694, 95% CI = -0.856 - -0.532, <0.001). The performance of other DM tests was not significantly less in either WMD or SMD. Patients with right TLE and with left TLE had no statistically significant difference in DM ability. An amygdala or (and) hippocampus resection might be related to more severe DM deficits. Various cognitive domains were related to decision-making capacity, although these correlations were not consistent across studies. CONCLUSION: Patients with epilepsy had poorer scores in avoid making risky decisions under ambiguity. Other types of DM ability might not be impaired; however, insufficient studies, with small samples, limited reliability of the results.

Altered spontaneous brain activity in MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder: A resting-state fMRI study.

OBJECTIVE: To investigate alterations in spontaneous brain activity in MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder using resting-state functional magnetic resonance imaging (RS-fMRI). METHODS: Eighteen MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder (PDD), 17 MRI-negative refractory temporal lobe epilepsy patients without major depressive disorder (nPDD), and 21 matched healthy controls (HC) were recruited from West China Hospital of SiChuan University from April 2016 to June 2017. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and 17-item Hamilton Depression Rating Scale were employed to confirm the diagnosis of major depressive disorder and assess the severity of depression. All participants underwent RS-fMRI scans using a 3.0T MRI system. MRI data were compared and analyzed using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) to measure spontaneous brain activity. These two methods were both used to evaluate spontaneous cerebral activity. RESULTS: The PDD group showed significantly altered spontaneous brain activity in the bilateral mesial prefrontal cortex, precuneus, angular gyrus, right parahippocampal gyrus, and right temporal pole. Meanwhile, compared with HC, the nPDD group demonstrated altered spontaneous brain activity in the temporal neocortex but no changes in mesial temporal structures. CONCLUSION: The PDD group showed regional brain activity alterations in the prefrontal-limbic system and dysfunction of the default mode network. The underlying pathophysiology of PDD may be provided for further studies.

Does pregnancy affect women with multiple sclerosis? A prospective study in Western China.

OBJECTIVES: Pregnancy is considered to be protective for multiple sclerosis (MS) but little is known about Asian MS women. Our study aimed to investigate whether pregnancy affects the course of MS and whether MS affects pregnancy in a Chinese cohort. METHODS: We established a database (2009-2016) of 94 females with MS in the Department of Neurology at West China Hospital. From this database, we enrolled females who had been pregnant before or after the clinical onset of MS and consecutively followed up the patients and their offspring for at least one year after delivery. We registered their demographic, clinical and pregnancy-related information, as well as the annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score. RESULTS: We enrolled 55 females with MS and 126 pregnancies. Among them, 14 females had 15 deliveries after MS onset. In these 15 full-term pregnancies after MS onset, the average ARR decreased from 0.46 ±â€¯0.52 in the year before pregnancy to 0.07 ±â€¯0.26 (P = .034) during pregnancy and no drug exposure were observed during pregnancy. The average EDSS score at one year after delivery (1.50 ±â€¯1.72) was higher than that at conception (0.77 ±â€¯1.35; P = .045). CONCLUSIONS: The natural history of MS during pregnancy suggests that full-term pregnancy protects MS females from relapse. However, the disability of MS females may develop after delivery.

Antiepileptic effect of olanzapine in epilepsy patients with atypical depressive comorbidity.

Depression is relatively common among patients with epilepsy, but often with predominant atypical symptoms. Some antiepileptic drugs show positive psychotropic effects, but these are not always sufficient to stabilize mood in epilepsy patients. Antidepressants are recommended to treat atypical depression but are not always effective and present a certain risk of seizure provocation. Thus, new treatment options are welcome. Here, we describe three cases of refractory epilepsy with atypical depression in which olanzapine, contrary to its earlier reported proconvulsant effect, showed excellent antidepressant action and resulted in seizure control. Possible mechanisms of this action are discussed.

Retinal nerve fiber layer thickness in optic neuritis with MOG antibodies: A systematic review and meta-analysis.

This meta-analysis aimed to systematically review current literature measuring the thickness of retinal nerve fiber layer (RNFL) in patients with myelin oligodendrocyte glycoprotein antibodies (MOG-ab) associated optic neuritis. Ten studies were enrolled and the results showed that the degree of RNFL loss in MOG-ab-positive optic neuritis patients may not differ from that of AQP4-ab patients. However, patients who were positive for MOG-ab showed more severe RNFL loss than those who were seronegative.

Altered composition of the gut microbiome in patients with drug-resistant epilepsy.

OBJECTIVE: The relationship between the gut microbiota and the central nervous system has been gradually recognized while whether microbiome plays a role in the pathogenesis of drug-resistant epilepsy is still unknown. The aim of our work was to explore whether dysbiosis is involved in the mechanism of drug-resistant epilepsy. METHODS: Patients with epilepsy attending West China Hospital of Sichuan University were enrolled from March to May 2017. Patients were grouped into drug-resistant (n = 42) and drug-sensitive (n = 49) groups, another 65 healthy controls were from the same families of the patients. The fecal samples were collected and the microbiome composition was analyzed by high-throughout sequencing of the 16s ribosomal DNA. RESULTS: We found that the gut microbial community of drug-resistant epilepsy was significantly altered with an abnormal increased abundance of rare flora. While the gut microbiome composition of drug-sensitive epilepsy was similar with that of healthy controls. Specifically, patients with four seizures per year or fewer showed an increase of Bifidobacteria and Lactobacillus than those with more than four seizures per year. CONCLUSIONS: Dysbiosis may be involved in the mechanism of drug-resistant epilepsy and restoring the gut microbial community may be a novel therapeutic method for drug-resistant epilepsy.

Reliability of information about the use of antiepileptic drugs during pregnancy from three major web search engines in China.

OBJECTIVES: The objective of this study was to assess the reliability of online information, as provided by three major search engines in China, about the usage of antiepileptic drugs (AEDs) during pregnancy. METHOD: Over eight weeks, six physicians conducted a literature search on six computers and six smartphones at a frequency of once per week. During each web search on each computer and smartphone, three major search engines in China were used, namely, Baidu, Sogou and 360. The search terms used were a combination of words, including one AED name (valproate/oxcarbazepine/levetiracetam/lamotrigine) and one Chinese word ("huaiyun" or "renshen", which means pregnancy in Chinese). The top ten websites retrieved from each search were recorded. After the content of each website was evaluated, the sites were categorized into 9 types. Meanwhile, commercial advertisements on each web page were also registered. RESULTS: A total of 16,411 search results were assessed. After excluding the redundant web pages, 4840 search results were included in the data analysis. Only 12.05% of the search results were reliable, 47.75% were partly reliable, and 40.21% were unreliable. A total of 4139 (85.52%) webpages contained commercial advertisements. The results from a multivariate analysis suggested that websites with no advertisements and professional websites have an independent positive impact on reliability. CONCLUSION: Overall, little information on AED usage during pregnancy provided by major search engines in China was reliable. PRACTICE IMPLICATIONS: Accurate and professional online information for female patients with epilepsy should be provided through major efforts by the government, search engine companies, professional websites and epilepsy physicians.

Relationship between right-to-left shunt and migraine in patients with epilepsy: a single-centre, cross-sectional study in China.

OBJECTIVES: To investigate the relationship between right-to-left shunt and migraine to account for the unexplained high prevalence of migraine in patients with epilepsy. DESIGN: This is a cross-sectional study. The diagnosis and interview process of patients with migraine was based on the International Classification of Headache Disorders-3 beta in patients with epilepsy. Participants underwent transthoracic echocardiography (TTE) with contrast medium to identify right-to-left shunt. The highest number of microbubbles were recorded in the left atrium before the complete microbubble outflow of the right atrium. A moderate-to-large shunt was defined as the presence of 10 or more microbubbles. SETTING: A single-centre, cross-sectional study in China, 2015-2017. PARTICIPANTS: Patients with epilepsy. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measures were the prevalence of migraine, the prevalence of right-to-left shunt in patients with migraine and those without migraine, and the prevalence of migraine in different degrees of shunting. RESULTS: Three hundred thirty-nine participants with epilepsy who completed TTE were included in the analysis. The overall prevalence of migraine was 23.0%. One-third of the migraineurs had mild right-to-left shunt and one-fifth of the migraineurs had moderate-to-large right-to-left shunt. Patients with mild shunt did not have a higher prevalence of migraine than those without shunt (26.3% vs 18.1%, p=0.102); however, a higher prevalence of migraine was found in patients with moderate-to-large shunt (39.0% vs 18.1%, OR=2.90, 95% CI=1.41 to 5.98, p=0.003). Patients with migraine and patients without migraine had similar prevalence of mild shunt; however, patients with migraine had more moderate-to-large shunt (20.5% vs 9.6%, p=0.002). Right-to-left shunt and female were factors predicting migraine prevalence. CONCLUSIONS: One-fifth of migraineurs were correlated with moderate-to-large right-to-left shunt which could be an underlying cause of migraine in epilepsy.