Short-term exposure to air pollution has previously been studied in relation to certain neurological disorders, but there is still a lack of convincing data linking air pollution to epileptic seizures. The study\'s goal was to investigate how exposure to ambient nitrogen dioxide (NO2) affected the number of patients seeking assistance at the Wuhan Emergency Medical Center due to epileptic seizures. We gathered data on medical emergency calls (MECs), daily ambient air pollution concentrations (SO2, NO2, PM2.5, PM10, CO, and O3), and meteorological variables in Wuhan, China, spanning from January 1, 2017, to November 30, 2019. To investigate the potential influence of ambient nitrogen dioxide on MECs for epileptic seizures, we carried out a time-series investigation using the general additive model (GAM). Additionally, analyses stratified by season, age, and gender were performed. A total of 8989 records of MECs for epileptic seizures were enrolled in our study during the period. Statistical analysis indicates that a rise of 10 μg/m3 in NO2 concentration is linked to a 0.17% increase in daily MECs for epileptic seizures (95% confidence interval [CI]: 0.02%, 0.32%). Furthermore, people aged 14-59 years were more susceptible(2.25%, P < 0.05). The short-term effects of NO2 exposure on daily MECs for epileptic seizures were stronger in warm seasons than in cool seasons (0.55% vs. -0.10%, P < 0.0001). Our findings suggests that short-term exposure to ambient NO2 was positively correlated with daily MECs for epileptic seizures in Wuhan, China. Additionally, we observed that these associations were stronger in patients aged above 14 but under 60 years and the warmer seasons (from April to September).

BACKGROUND: Saffron, a traditional Chinese medicine, is derived from Crocus sativus L. stigmas and has been reported to possess neuroprotective properties and potentially contribute to the inhibition of apoptosis and inflammation. Safranal, a potent monothyral aldehyde, is a main component of saffron that has been reported to have antiepileptic activity. However, the specific mechanism by which safranal suppresses epileptic seizures via its antiapoptotic and anti-inflammatory properties is unclear.
OBJECTIVE: To evaluate the effect of safranal on seizure severity, inflammation, and postictal neuronal apoptosis in a mouse model of pentetrazole (PTZ)-induced seizures and explore the underlying mechanism involved.
METHODS: The seizure stage and latency of stage 2 and 4 were quantified to assess the efficacy of safranal in mitigating PTZ-induced epileptic seizures in mice. Electroencephalography (EEG) was employed to monitor epileptiform afterdischarges in each experimental group. The cognitive abilities and motor functions of the mice were evaluated using the novel object recognition test and the open field test, respectively. Neurons were quantified using hematoxylin and eosin staining. Additionally, bioinformatics tools were utilized to predict the interactions between safranal and specific target proteins. Glycogen synthase kinase-3β (GSK-3β), mitochondrial apoptosis-related proteins, and inflammatory factor levels were analyzed through western blotting. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) concentrations in brain tissue were assessed by ELISA.
RESULTS: Safranal decreased the average seizure stage and increased the lantency of stage 2 and 4 seizures in PTZ-induced epileptic mice. Additionally, safranal exhibited neuroprotective effects on hippocampal CA1 and CA3 neurons and reduced hyperactivity caused by postictal hyperexcitability. Bioinformatics analysis revealed that safranal can bind to five specific proteins, including GSK-3β. By promoting Ser9 phosphorylation and inhibiting GSK-3β activity, safranal effectively suppressed the NF-κB signaling pathway. Moreover, the findings indicate that safranal treatment can decrease TNF-α and IL-1β levels in the cerebral tissues of epileptic mice and downregulate mitochondrial apoptosis-related proteins, including Bcl-2, Bax, Bak, Caspase 9, and Caspase 3.
CONCLUSIONS: Safranal can suppress the NF-κB signaling pathway and mitochondrial-dependent apoptosis through GSK-3β inactivation, suggesting that it is a promising therapeutic agent for epilepsy treatment.

BACKGROUND: Epilepsy is a neurological disorder that presents with recurring and spontaneous seizures. It is prevalent worldwide, affecting up to 65 million people, with 80% of cases found in lower-income countries. Medicinal plants are commonly employed for managing and treating epilepsy and convulsions due to their unique therapeutic properties. With increasing research and clinical application, medicinal plants are gaining attention globally due to their potent therapeutic effects and fewer side effects. The development of new plant-based antiepileptic/anticonvulsant agents has become a major focus in the pharmaceutical industry.
OBJECTIVE: This article summarizes recent research on medicinal plants with reported antiepileptic/anticonvulsant effects. It provides pharmacological and molecular mechanism of action information for the crude extracts and related active constituents evaluated in preclinical research for the treatment of epilepsy and convulsions, and offers a reference for the development of future related studies in this area.
METHODS: Articles related to ethnopharmacological and antiepileptic studies on plants or natural products from 2018 to 2023 were collected from PubMed, Web of Science and Scopus, etc. using keywords related to epilepsy, medicinal plants, and natural products, etc. RESULTS: Eighty plant species are commonly used to treat epilepsy and convulsions in African and Asian countries. Sixty natural products showing potential for antiepileptic/anticonvulsant effects have been identified from these medicinal plants. These products can be broadly classified as alkaloids, coumarins, flavonoids, saponins, terpenoids and other compounds. The antiepileptic action of plant extracts and their active ingredients can be classified according to their abilities to modulate the GABAergic and glutamatergic systems, act as antioxidants, exhibit anti-neuroinflammatory effects, and provide neuroprotection. In addition, we highlight that some medicinal plants capable of pharmacologically relieving epilepsy and cognition may be therapeutically useful in the treatment of refractory epilepsy.
CONCLUSIONS: The review highlights the fact that herbal medicinal products used in traditional medicine are a valuable source of potential candidates for antiepileptic drugs. This confirms and encourages the antiepileptic/anticonvulsant activity of certain medicinal plants, which could serve as inspiration for further development. However, the aspects of structural modification and optimization, metabolism, toxicology, mechanisms, and clinical trials are not fully understood and need to be further explored.

Impaired activation and regulation of the extinction of inflammatory cells and molecules in injured neuronal tissues are key factors in the development of epilepsy. SerpinA3N is mainly associated with the acute phase response and inflammatory response. In our current study, transcriptomics analysis, proteomics analysis, and Western blotting showed that the expression level of Serpin clade A member 3N (SerpinA3N) is significantly increased in the hippocampus of mice with kainic acid (KA)-induced temporal lobe epilepsy, and this molecule is mainly expressed in astrocytes. Notably, in vivo studies using gain- and loss-of-function approaches revealed that SerpinA3N in astrocytes promoted the release of proinflammatory factors and aggravated seizures. Mechanistically, RNA sequencing and Western blotting showed that SerpinA3N promoted KA-induced neuroinflammation by activating the NF-κB signaling pathway. In addition, co-immunoprecipitation revealed that SerpinA3N interacts with ryanodine receptor type 2 (RYR2) and promotes RYR2 phosphorylation. Overall, our study reveals a novel SerpinA3N-mediated mechanism in seizure-induced neuroinflammation and provides a new target for developing neuroinflammation-based strategies to reduce seizure-induced brain injury.

Epilepsy is a common neurological disorder characterized by recurring seizures, but its underlying mechanisms remain poorly understood. Despite extensive research, there are still gaps in our knowledge about the relationship between brain dynamics and seizures. In this study, our aim is to address these gaps by proposing a novel approach to assess the role of brain network dynamics in the onset of seizures. Specifically, we investigate the relationship between brain dynamics and seizures by tracking the distance to criticality. Our hypothesis is that this distance plays a crucial role in brain state changes and that seizures may be related to critical transitions of this distance. To test this hypothesis, we develop a method to measure the evolution of the brain network\'s distance to the critical dynamic systems (i.e., the distance to the tipping point, DTP) using dynamic network biomarker theory and random matrix theory. The results show that the DTP of the brain decreases significantly immediately after onset of an epileptic seizure, suggesting that the brain loses its well-defined quasi-critical state during seizures. We refer to this phenomenon as the \"criticality of the criticality\" (COC). Furthermore, we observe that DTP exhibits a shape transition before and after the onset of the seizures. This phenomenon suggests the possibility of early warning signal (EWS) identification in the dynamic sequence of DTP, which could be utilized for seizure prediction. Our results show that the Hurst exponent, skewness, kurtosis, autocorrelation, and variance of the DTP sequence are potential EWS features. This study advances our understanding of the relationship between brain dynamics and seizures and highlights the potential for using criticality-based measures to predict and prevent seizures.

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The congenital disorder of glycosylation associated with ALG1 (ALG1-CDG) is a rare autosomal recessive disease. Due to the deficiency of β1,4 mannosyltransferase caused by pathogenic variants in ALG1 gene, the assembly and processing of glycans in the protein glycosylation pathway are impaired, resulting in a broad clinical spectrum with multi-organ involvement. To raise awareness of clinicians for its manifestations and genotype, we here reported a new patient with a novel variant in ALG1 gene and reviewed the literature to study the genotype-phenotype correlation.
Clinical characteristics were collected, and clinical exome sequencing was used to identify the causative variants. MutationTaster, PyMol, and FoldX were used to predict the pathogenicity, changes in 3D model molecular structure of protein, and changes of free energy caused by novel variants.
The proband was a 13-month-old Chinese Han male characterized by epileptic seizures, psychomotor development delay, muscular hypotonia, liver and cardiac involvement. Clinical exome sequencing revealed the biallelic compound heterozygosity variants, a previously reported variant c.434G>A (p.G145N, paternal) and a novel variant c.314T>A (p.V105N, maternal). The literature review found that in severe phenotypes, the incidences of clinical manifestations were significantly higher than that in mild phenotypes, including congenital nephrotic syndrome, agammaglobulinemia, and severe hydrops. Homozygous c.773C>T was a strongly pathogenic variant associated with a severe phenotype. When heterozygous for c.773C>T, patients with another variant leading to substitution in amino acids within the strongly conserved regions (c.866A>T, c.1025A>C, c.1182C>G) may cause a more severe phenotype than those within less-conserved regions (c.434G>A, c.450C>G, c.765G>A, c.1287T>A). c.1129A>G, c.1076C>T, and c.1287T>A were more likely to be associated with a mild phenotype. The assessment of disease phenotypes requires a combination of genotype and clinical manifestations.
The case reported herein adds to the mutations identified in ALG1-CDG and a review of this literature expands the study of the phenotypic and genotypic spectrum of this disorder.

Human herpesvirus 7 (HHV-7) is a common virus that infects children early and is accompanied by lifelong latency in cells, which is easy to reactivate in immunodeficient adults, but the underlying pathological mechanism is uncertain in immunocompetent adults without peculiar past medical history. Even though the clinical manifestation of the encephalitis caused by HHV-7 is uncommon in immunocompetent adults, the HHV-7 infection should not be neglected for encephalitis for unknown reasons.
We reported here a case of HHV-7 encephalitis with epileptic seizures. While the brain computer tomography was standard, electroencephalography displayed slow waves in the temporal and bilateral frontal areas, then HHV-7 DNA was detected in the metagenomic next-generation sequencing of cerebrospinal fluid. Fortunately, the patient recovered after treatment and was discharged 2 months later. We also collected the related cases and explored a better way to illuminate the underlying mechanism.
The case indicates clinicians should memorize HHV-7 as an unusual etiology of encephalitis to make an early diagnosis and therapy.

This observational retrospective study was conducted on patients with epilepsy (PWE) in China who had at least one dose of COVID-19 vaccine and it investigated the safety of vaccination by analyzing changes in epileptic seizures and their influencing factors. Consecutive PWE who were followed up in the epilepsy clinic between June 2021 and May 2022 were enrolled. Data on vaccine type, demographic information, clinical characteristics of epilepsy, and treatment were collected through a questionnaire survey and retrospectively analyzed. PWE were divided into a stable seizure group and a worsening seizure group based on seizure episodes at least 90 days after the first vaccine dose. A total of 79 PWE were included. After vaccination, 14 patients (17.7%) had worsening seizures, 92.9% of whom had an increased seizure frequency. Compared with patients in the stable seizure group, patients in the worsening seizure group had significant differences in baseline monthly seizure frequency (P = .012), improper antiseizure medication (ASM) administration (P = .003) and a disrupted sleep routine (P = .016). Multivariate logistic regression analysis showed that improper ASM administration (OR 6.186, 95% confidence interval [CI] 1.312-29.170; p = .021) and a disrupted sleep routine (OR 6.326, 95% CI 1.326-30.174; p = .021) were significantly associated with seizure worsening. In short, COVID-19 vaccination is safe for PWE, and only those with poor seizure control have the possibility of seizure exacerbation after COVID-19 vaccination. The vaccination per se does not represent a major influencing factor, but the improper use of ASMs and a disrupted sleep routine may be correlated with seizure aggravation after vaccination.

Clinical and experimental data hints that prolonged and repeated epileptic seizures can lead to molecular, biochemical, metabolic, and structural changes in the brain, a continuous process of chronic brain injury that ultimately leads to neuronal death. The histological characteristics of hippocampal structure determine its high sensitivity to excitotoxicity and present different types of neuronal death, including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis. Hippocampal neuronal death promotes the progression of epileptogenesis, seizures, and epilepsy and is closely related to the impairment of cognitive function. Massive evidence indicates that oxidative stress plays a critical role in different forms of neuronal death induced by epileptic seizures. The brain is particularly vulnerable to damage caused by oxidative stress, and an increase in oxidative stress biomarkers was found in various epilepsy types. The purpose of this review is to elucidate the molecular mechanism of neuronal death and explore the moderating effect of oxidative stress on epileptic seizure-induced neuronal death patterns so as to find potential intervention targets for neuroprotective treatment after epileptic seizures.