Anti-Seizure Monotherapy and Early Abortion Under Real-World Conditions.

Background: Most pregnant epilepsy patients need to continue using anti-seizure medications (ASMs) to control epileptic seizures. Objective: This study aimed to evaluate the risk of early abortion in pregnant epilepsy patients exposed to anti-seizure monotherapy. Methods and Material: We prospectively followed up pregnant epilepsy patients treated with anti-seizure monotherapy in our epilepsy center between January 2010 and January 2020 under real-world conditions. Early abortion (spontaneous abortion in the first trimester of pregnancy) was the endpoint. Results: Of 211 pregnancies exposed to monotherapy, including 40% (n = 85) to lamotrigine (LTG), 28% (n = 58) to oxcarbazepine (OXC), 15% (n = 32) to sodium valproate (VPA), 9% (n = 19) to levetiracetam, and 8% (n = 17) to carbamazepine, six ended in early abortion. The overall risk of early abortion in pregnant patients exposed to ASM monotherapy was 2.8% (n = 6) [95% confidence interval (CI) = 0.013-0.073]. The risk of early abortion was 2.4% (n = 2) (95% CI = 0.003-0.082) in women treated with LTG, 3.5% (n = 2) (95% CI = 0.004-0.115) in women treated with OXC, and 6.3% (n = 2) (95% CI = 0.008-0.208) in women treated with VPA. The relative risk of early abortion in the LTG, OXC, and VPA groups did not reach statistical significance. Conclusions: Although the sample size of our study was small, these results indicate that the use of anti-seizure monotherapy in pregnant epilepsy patients may not increase the risk of early miscarriage. Larger prospective studies are needed for sufficient statistical analysis.

Levetiracetam induces severe psychiatric symptoms in people with epilepsy.

BACKGROUND: Drug-induced psychiatric symptoms are an important cause of treatment failure. Worldwide, levetiracetam has been widely used to treat epilepsy; however, associated psychobehavioral abnormalities have been observed . This study aimed to characterize levetiracetam-induced severe psychiatric symptoms and to propose preventive and therapeutic measures. METHODS: In this retrospective cluster sampling study, psychiatric symptoms of patients who had taken levetiracetam for at least 1 month were analyzed. RESULTS: 111(7.8%) of the 1,412 included patients exhibited severe psychiatric symptoms. Hallucinations, delusions, aggressive behavior, and agitation were the most common manifestations . Some patients also showed suicidal and self-harm behaviors. These symptoms were mainly controlled by reducing the dose of levetiracetam, stopping the drug, or adding antipsychotic drugs to the treatment regimen. CONCLUSION: The severe psychiatric symptoms caused by levetiracetam require special attention.

Beclin1 Deficiency Suppresses Epileptic Seizures.

Epilepsy is a common disease of the nervous system. Autophagy is a degradation process involved in epilepsy, and in turn, seizures can activate autophagy. Beclin1 plays a critical role in autophagy and participates in numerous physiological and pathological processes. However, the mechanism underlying the effect of Beclin1 on epilepsy remains unclear. In this study, we detected increased expression of Beclin1 in brain tissues from patients with temporal lobe epilepsy (TLE). Heterozygous disruption of beclin1 decreased susceptibility to epilepsy and suppressed seizure activity in two mouse epilepsy models. We further illustrated for the first time that heterozygous disruption of beclin1 suppresses excitatory synaptic transmission, which may be caused by a decreased dendritic spine density. These findings suggest for the first time that the regulation of Beclin1 may serve as a strategy for antiepileptic therapy. In addition, Beclin1 participates in synaptic transmission, and the development of dendritic spines may be a biological function of Beclin1 independent of its role in autophagy.

Intestinal Klebsiella pneumoniae infection enhances susceptibility to epileptic seizure which can be reduced by microglia activation.

Epilepsy is a common nervous system disease, and the existing theory does not fully clarify its pathogenesis. Recent research suggests that intestinal microbes may be involved in the development of epilepsy, but which microbe is involved remains unclear. We used 16s rRNA sequencing to identify the most relevant gut microbe. To determine the relationship between this microbe and epilepsy, we used an animal model. In addition, western blotting and immunofluorescence, as well as inhibitor studies, were used to evaluate and confirm the role of microglia in this process. In this study, we first report an increase in gut Klebsiella pneumoniae in patients with epilepsy. Subsequently, animal studies revealed that Klebsiella pneumoniae in the intestinal tract affects seizure susceptibility and activates microglial cells to release inflammatory factors. Furthermore, the inflammatory response of microglial cells plays a protective role in the seizure susceptibility caused by an increased abundance of Klebsiella pneumoniae. Our results suggest that gut disruption may be involved in seizure regulation and microglia protect the brain against seizure under this condition. These findings provide a new perspective for research on the pathogenesis and prevention of epilepsy.

Grassland ecological restoration based on the relationship between vegetation and its below-ground habitat analysis in steppe coal mine area.

Coal mining activities have caused severe disturbances to the regional ecosystem and soil properties. Studying the relationship of vegetation and its below-ground habitat (RVBGH) is of great significance to the coal mine land ecological restoration. To identify the optimal thickness of the soil layer for mine land ecosystem recovery and characterize the changes of the reclaimed soil-vegetation ecosystem, we studied natural and reclaimed grassland at the coal mine of Baorixile, located in Hulunbuir Steppe, Northeastern China. The vegetation and its below-ground habitat (BGH), including "root mass" and soil properties in the soil profile (0-100 cm), were surveyed in the natural and different year-reclaimed grassland. The "root mass" is the part of root system that has the most amounts of root hairs, which is the functional zone for plant growth. The RVBGH was identified by the "root mass" and plant water extraction depth, measured through the isotope δD and δ18O method. Firstly, the BGH of natural grassland was identified as a "double layer" vertical structure, with the "root mass" of 37.11 ± 2.57% fine roots at 0-20 cm range and 30.44 ± 2.67% at 20-40 cm range. The annual and perennial plant "root mass" was found at 0-20 cm and 20-40 cm depth, respectively. Secondly, an optimal thickness of the soil covering of 30-40 cm was proposed for grassland reclamation. Thirdly, along the reclamation chronosequence, the values of the reclaimed vegetation properties (height, density, coverage and diversity) increased and a deep root system was established. The "root mass" increased from one layer to double layer and the amount of total fine roots increased from 1621 ± 231.9 to 4459 ± 456.0. Moreover, the reclaimed soil properties of organic matter, cation exchange capacity, available N and P also increased. The study proposed that vegetation restoration was significantly correlated with its BGH, suggesting that vegetation BGH recovery is crucial in ecological restoration.

Response to antiepileptic drugs after unsuccessful epilepsy surgery: A multivariate analysis of 103 patients.

OBJECT: Epilepsy patients may still have seizures after surgery, and there have been few studies on the response to antiepileptic drugs (AEDs) after surgery failure. The purpose of this study was to analyze the response to AEDs after unsuccessful epilepsy surgery. METHODS: Patients who underwent unsuccessful epilepsy surgery between January 1999 and January 2019 were evaluated. Patient demographics, etiology, factors related to surgery and AED use patterns were assessed. RESULTS: After excluding the 5 patients who were lost to follow-up and the 2 patients who died, the records of 103 consecutive patients were analyzed. Ninety patients (87.4 %) had seizure recurrence within one year after surgery, 2 (1.9 %) patients had recurrence from one year to two years after surgery, and 11 (10.7 %) patients had recurrence two or more years after surgery (2-10 years). After surgery failure, the patients tried at least 2 kinds of AEDs with different mechanisms for more than 2 years. The average total number of AEDs used was 5.97, the average number of AEDs used before surgery was 3.21, and the average number of AEDs used after surgery was 4.02. After retreatment with AEDs, 10 patients (9.7 %) were seizure-free, 18 patients' (17.5 %) seizures were alleviated, and 75 patients (72.8 %) had seizures as they did prior to the adjustments. The number of AEDs used before and after surgery and the total number of AEDs were not significantly different among the seizure free group, alleviated seizure group and no change group. There were no significant differences in seizure onset age, surgery age, etiology, time between seizure onset and surgery, magnetic resonance imaging, seizure type, localization and lateralization of the surgery site among the three groups. CONCLUSIONS: The results showed that a small percentage of patients (27.2 %) who undergo unsuccessful epilepsy surgery benefit from AED adjustments; however, the vast majority of patients (72.8 %) do not benefit from AED adjustments.

Groundwater environmental risk assessment of abandoned coal mine in each phase of the mine life cycle: a case study of Hongshan coal mine, North China.

Human activities during each phase of coal mine life cycle greatly affect groundwater environment. The groundwater environment destruction is not just only the destruction of underground structure but also the social problems caused by available groundwater resources reduction, as well as the environmental problems affecting ecosystem and human health. Moreover, the groundwater environmental risk of coal mining is complex, dynamic, and long-term. Therefore, a framework and quantitative method for groundwater environmental risk analysis at different phases of the mine life cycle was presented, which is composed of the groundwater system destruction risk (GSDR) and social-economic-ecological vulnerability (SEEV) assessment. The framework was applied in Hongshan abandoned coal mine, North China. Based on the aquifer structure destruction, groundwater flow field evolution, contamination, and social-economic influence analysis, 12 main controlling factors for the GSDR and 7 factors for the SEEV were determined and quantified separately. The results showed that the groundwater contamination of the Hongshan mine mainly occurred after closure, caused by the cross-strata pollution of mine water, which significantly reduced the groundwater available resources, which greatly affected local social-economy sustainable development and residents' health. The Hongshan mine closure increased groundwater environmental risk, with the GSDR high-risk zone being 12.51 km2 larger than that during the mining phase and the SEEV was calculated at a high level. This framework promotes systematic integration of the groundwater environmental risk assessment in mine life cycle.

A Rare KIF1A Missense Mutation Enhances Synaptic Function and Increases Seizure Activity.

Although genetic factors are considered a main etiology of epilepsy, the causes of genetic epilepsy in the majority of epilepsy patients remain unknown. Kinesin family member 1A (KIF1A), a neuron-specific motor protein that moves along with microtubules, is responsible for the transport of membranous organelles and synaptic vesicles. Variants of KIF1A have recently been associated with hereditary spastic paraplegia (HSP), hereditary sensory and autonomic neuropathy type 2 (HSANII), and intellectual disability. However, mutations in KIF1A have not been detected in patients with epilepsy. In our study, we conducted customized sequencing of epilepsy-related genes of a family with six patients with generalized epilepsy over three generations and identified a rare heterozygous mutation (c.1190C > A, p. Ala397Asp) in KIF1A. Whole-cell recordings from primary cultured neurons revealed that the mutant KIF1A increases the excitatory synaptic transmission but not the intrinsic excitability of neurons, and phenotype testing in zebrafish showed that this rare mutation results in epileptic seizure-like activity. These results provide new evidence demonstrating that KIF1A dysfunction is involved in epileptogenesis.

Effects of seizure frequency, depression and generalized anxiety on suicidal tendency in people with epilepsy.

PURPOSE: The highest risk of suicide was identified among patients diagnosed with both epilepsy and comorbid psychiatric disease. The most common comorbid psychiatric conditions of epilepsy are anxiety and depression. This study examines whether and how seizure frequency, depression and generalized anxiety interact to influence suicidal tendency. METHODS: A consecutive cohort of PWE was recruited from the First Affiliated Hospital of Chongqing Medical University. Each patient completed the Neurological Disorders Depression Inventory for Epilepsy scale[NDDI-E], the Generalized Anxiety Disorder-7 (GAD-7), and the suicidality module of Mini-International Neuropsychiatric Interview(MINI) v.5.0.0. Spearman's correlation and moderated mediation analysis were used to examine the associations among seizure frequency, depression, generalized anxiety and suicidal tendency. RESULTS: Seizure frequency was positively associated with suicidal tendency. Depression severity partially mediated the relationship between seizure frequency and suicidal tendency. The indirect effect of seizure frequency on suicidal tendency was positive, and accounted for 50.2 % of the total effect of seizure frequency on suicidal tendency. The indirect effect of seizure frequency on suicidal tendency through depression severity was positively moderated by generalized anxiety severity. CONCLUSIONS: Reducing seizure frequency may be the basis of suicide prevention in PWE. At the same time, the effect of seizure frequency on suicidal tendency can be partially explained by the mediation of depression severity, and the magnitude of the indirect effect of seizure frequency on suicidal tendency was contingent upon generalized anxiety severity. In addition to depression severity, generalized anxiety severity also exerts an important effect on suicidal tendency in PWE.