BackgroundThis study was conducted to determine the prevalence of epilepsy in Daofu County, Sichuan Province, China, and to identify factors associated with comorbid depression, anxiety, and impaired quality of life among people with epilepsy (PWE).MethodsIn this community-based, cross-sectional study, a door-to-door survey of epilepsy was performed among 37,390 permanent residents of Daofu County. The survey identified 164 confirmed cases of epilepsy. Of them, 127 participants (aged ≥ 16 years) who were able to complete self-reported questionnaires were enrolled for final analysis. Depression and anxiety symptoms were assessed using the Chinese versions of the Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E) and the Generalized Anxiety Disorder-7 (GAD-7) scale, respectively. Health-related quality of life was evaluated with the Quality of Life in Epilepsy Inventory-31 (QOLIE-31). Factors associated with depression and anxiety were examined using logistic regression analyses, while factors influencing QOLIE-31 scores were assessed by linear regression.ResultsThe estimated prevalence of epilepsy in Daofu County was 4.4‰ (95% CI: 3.7–5.1‰). Independent factors associated with the comorbid depression included a low monthly household income per capita (aOR = 4.41, 95% CI: 1.82–10.71; P = 0.001) and active epilepsy (aOR = 4.87, 95% CI: 1.74–13.62; P = 0.003). Independent factors associated with the comorbid anxiety included a low monthly household income per capita (aOR = 5.03, 95% CI: 1.88–13.5; P = 0.001) and active epilepsy (aOR = 4.84, 95% CI: 1.95–12.01; P = 0.001). Furthermore, factors including a low monthly household income per capita, a history of status epilepticus, and active epilepsy were significantly associated with a lower QOLIE-31 score.ConclusionsThere is a high burden of depression and anxiety among PWE in the Tibetan areas of China. Active epilepsy is the most potent, independent risk factor of psychiatric comorbidities and poorer quality of life. These findings suggest the urgent need for integrated epilepsy management and mental health services in this resource-limited region.

Deep brain stimulation (DBS) has emerged as an important therapeutic intervention, effectively addressing a spectrum of drug-resistant neurological and psychiatric disorders. Although its efficacy has been validated in adult populations, the current literature reveals a significant gap concerning its application in pediatric patients. Specifically, pediatric populations afflicted with severe conditions such as dystonia, drug-resistant epilepsy, Tourette syndrome, and some other neuropsychiatric conditions demonstrate an urgent need for alternative therapeutic options. This review systematically examined the existing literature on the application of DBS in pediatric neurological disorders, focusing on the aforementioned conditions. Preliminary findings indicate that while DBS shows potential for a specific subset of pediatric patients, the current data is limited and lacks statistical power. Reported cases exhibit varying degrees of therapeutic success. Although adverse effects associated with DBS in pediatric populations are rare, further investigation is essential to define safety profiles accurately. Future research should focus on conducting large-scale, randomized controlled trials to validate outcomes and determine optimal patient selection criteria, thereby broadening its clinical application within the pediatric population.

BackgroundStereotactic electroencephalography (SEEG) has emerged as a widely utilized diagnostic approach in epilepsy surgery, demonstrating broad clinical applications and a favorable safety profile. SEEG, when combined with radiofrequency thermocoagulation (RF-TC), facilitates the identification of epileptogenic zones and serves as a therapeutic option that eliminates the need for general anesthesia, thus incuring no additional costs for patients. This study aimed to investigate whether SEEG-guided RF-TC provides early therapeutic benefits.MethodsA retrospective analysis was performed on 44 patients with drug-resistant epilepsy who underwent RF-TC treatment between April 2019 and December 2022, with complete follow-up data available. RF-TC was administered after the recording three or more habitual epileptic seizures in all patients. Demographic characteristics were retrospectively assessed, and treatment outcomes were evaluated using the Engel classification system.ResultsSEEG-guided RF-TC treatment was successfully performed in all patients without significant neurological complications. An average of 7.7 ± 0.4 electrodes were implanted per patient, with a SEEG monitoring duration of 7.5 days (range: 6.8–11). Follow-up after thermocoagulation ranged from 9 to 63 months. At the three-month follow-up, 56.8% of patients achieved Engel I (11 cases) and II (14 cases) were included. At the six-month follow-up, 40.9% of patients achieved Engel grades I (9 cases) and II (9 cases), with five patients proceeding to surgical treatment. By the 12-month follow-up, 40.9% of patients reached Engel grades I (5 cases) and II (13 cases), with a cumulative total of 12 patients undergoing surgical intervention. At the 24-month follow-up, 20.5% of patients achieved Engel grades I (3 cases) and II (6 cases), resulting in a cumulative total of 16 patients undergoing surgical treatment. A statistically significant reduction in seizure frequency was observed before and after thermocoagulation in all 44 patients (P = 0.007), although the therapeutic effect of thermocoagulation decreased over time.ConclusionsSEEG-guided RF-TC is a safe and effective treatment modality for drug-resistant epilepsy. However, as follow-up duration increases, both seizure-free rates and response rates following RF-TC progressively decline.

BackgroundThe Midasin AAA (ATPase associated with various activities) ATPase 1 (MDN1) gene, a member of the AAA protein family, plays a crucial role in ribosome maturation. MDN1 is expressed in the human brain throughout life, especially during early development and adulthood. However, MDN1 variants have not been previously reported in patients with epilepsy. This study aims to explore the association between MDN1 variants and epilepsy.MethodsTrios-based whole-exome sequencing was performed in a cohort of patients with epilepsy susceptibility from the China Epilepsy Gene 1.0 Project. The excess, damaging effects, and molecular subregional implications of variants, as well as the spatio-temporal expression of MDN1, were analyzed to validate the gene-disease association.ResultsCompound heterozygous variants in MDN1 were identified in five unrelated patients with febrile seizures or secondary epilepsy. Three patients presented with febrile seizures/epilepsy with febrile seizures plus, while two patients developed epilepsy secondary to brain damage (five or seven years after). These variants were either absent or present at low frequencies in the control group, and exhibited statistically significant higher frequencies in the case group compared to controls. All the missense variants were predicted to be damaging by at least one in silico tool. In each pair of compound heterozygous variants, one allele was located in the AAA2-AAA3 domains, while the other allele was located in the linker domain or its vicinity. In contrast, most of the variants from the asymptomatic control group were located outside the AAA domains, suggesting a molecular subregional implication of the MDN1 variants.ConclusionsMDN1 is potentially a susceptibility gene for epilepsy.

BackgroundHemorrhagic stroke has a high incidence, often leaving patients with significant complications such as limb mobility disorders after treatment. Traditional treatment methods for stroke patients mainly include limb function exercises and hyperbaric oxygen therapy, which have shown effective results. In recent years, there have been reports utilizing vagus nerve stimulation (VNS) to treat limb paralysis in ischemic stroke patients, achieving encouraging outcomes. However, there are rare related reports on hemorrhagic stroke.Case presentationThis report presents a case of a patient who developed left upper limb hemiplegia and recurrent seizures after a hemorrhagic stroke. The patient showed a poor response to standard anti-epileptic treatment and was diagnosed with stroke-related epilepsy. To manage the recurrent seizures, VNS was performed. After the device was activated, the patient reported a significant reduction in abnormal muscle tone and increased mobility impairment in the affected upper limb. Parameters were adjusted, and intermittent stroke electrical stimulation was combined with upper limb rehabilitation exercises. After three months of active treatment, the patient’s seizures were well controlled, and there was significant improvement in upper limb function.ConclusionsVNS has potential in the rehabilitative treatment of stroke patients with upper limb dysfunction. It is hoped that more patients will benefit from this advanced treatment method in the future, regaining their health and vitality. Additionally, future research needs to further explore the mechanisms and methods of brain remodeling to provide theoretical support and more effective treatment options for stroke patient rehabilitation.

Genetic developmental and epileptic encephalopathies (DEE) are often associated with movement disorders. Accurate identification and classification of movement disorders are essential for management of these diseases. In this review, we describe the characteristics of various movement disorders associated with DEE and summarize the distribution of common DEE-related gene mutations reported in previous studies, aiming to provide references for the diagnosis and treatment of these disorders.

Epilepsy, characterized by recurrent seizures, is influenced by biological rhythms, such as circadian, seasonal, and menstrual cycles. These rhythms affect the frequency, severity, and timing of seizures, although the precise mechanisms underlying these associations remain unclear. This review examines the role of biological clocks, particularly the core circadian genes Bmal1, Clock, Per, and Cry, in regulating neuronal excitability and epilepsy susceptibility. We explore how the sleep-wake cycle, particularly non-rapid eye movement sleep, increases the risk of seizures, and discuss the circadian modulation of neurotransmitters like gamma-aminobutyric acid and glutamate. We explore clinical implications, including chronotherapy which refers to the practice of timing medical treatments to align with the body's natural biological rhythms, such as the circadian rhythm. Chronotherapy aligns anti-seizure medication administration with biological rhythms. We also discuss rhythm-based neuromodulation strategies, such as adaptive deep brain stimulation, which may dynamically change stimulation in response to predicted seizures in patients, provide additional therapeutic options. This review emphasizes the potential of integrating biological rhythm analysis into personalized epilepsy management, offering novel approaches to optimize treatment and improve patient outcomes. Future research should focus on understanding individual variability in seizure rhythms and harnessing technological innovations to enhance seizure prediction, precision treatment, and long-term management.

BackgroundThe SLC2A1 gene plays a vital role in brain energy metabolism. SLC2A1 variants have been reported to be associated with early-onset refractory seizures. This study aims to explore the association between the SLC2A1 gene and late-onset epilepsy.MethodsTrios-based whole-exome sequencing was performed on patients with epilepsy without acquired etiologies. The pathogenicity of the variants was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines.ResultsA total of 14 heterozygous SLC2A1 variants were identified in 16 unrelated families. The variants were evaluated as “pathogenic” or “likely pathogenic” according to the ACMG guidelines. Ten cases (62.5%) presented with infantile onset seizures and developmental delay/intellectual disability and were diagnosed with developmental and epileptic encephalopathy (DEE). The other six cases (37.5%) exhibited late-onset seizures and normal development. They were diagnosed with idiopathic partial epilepsy (n = 2) or idiopathic generalized epilepsy (n = 4). Further analysis showed that DEE-associated variants tended to cluster in the transmembrane region, whereas the mild epilepsy-associated variants tended to locate in regions outside the transmembrane region, suggesting a potential molecular sub-regional effect. A total of 15 cases had delayed diagnosis, with the longest delay being 22 years. The SLC2A1 expression stage, which is expressed at relatively high level throughout the whole life span, from the embryonic to adult stages with two peaks at approximately four and 14 years, is generally consistent with the seizure onset age. In addition, patients with early-onset age had variants that were potentially associated with severe damage, suggesting a potential correlation between the age of disease onset and the damaging effects of the variants.ConclusionsSLC2A1 variants are associated with late-onset epilepsy, which is consistent with the genetic-dependent stage feature of SLC2A1. Early genetic diagnosis is important for treatment of patients with SLC2A1 variants.

BackgroundTemporal lobe epilepsy is the most common type of focal epilepsy, but hereditary factors are usually overlooked. Reelin (RELN) is considered to be the second most common pathogenic gene implicated in autosomal dominant lateral temporal epilepsy (ADLTE). However, this mutation is not frequently discovered in the Chinese population. Additionally, there are few clinical studies regarding the connection between RELN and glioma.Case presentationThe healthcare records of an 8-year-old child who experienced generalized tonic-clonic seizures (GTCS) during sleep for 7 years were retrospectively analyzed. In addition to experiencing his first seizure at the age of one, his mother also suffered from GTCS during her pregnancy, and a glioma was discovered. An investigation involving gene sequencing was conducted on the proband and his parents. He was diagnosed with ADLTE once a missense mutation in RELN (c.1799 C > T) was identified as the causal factor. The mutation was inherited from his mother. He was taking levetiracetam (500 mg twice a day) to avoid seizures, but his mother died of status epilepticus caused by glioma recurrence two years earlier.ConclusionsGenetic issues should be given more consideration in cases of temporal lobe epilepsy. If the source of the seizures is determined to be inherited, anti-seizure medications should be used for prolonged periods. Furthermore, more research is required to determine whether mutations in RELN are related to the occurrence and progression of gliomas.

BackgroundRecent studies suggest that hypertension may increase the risk of epilepsy onset, revealing intricate interactions between cardiovascular health and neurological disorders, thus emphasizing the significance of conducting further investigations into their connection. This study aimed to investigate the potential causality between hypertension, either in systolic or diastolic blood pressure, and epilepsy, using a Mendelian randomization strategy.MethodsA two-sample Mendelian randomization design was used in this study. We extracted data from the UK Biobank, FinnGen, and the International Consortium of Blood Pressure, utilizing blood pressure-related single nucleotide polymorphisms as instrumental variables to evaluate the influence of hypertension on the risk of epilepsy. Inverse variance weighted, weighted median, and MR-Egger approaches were used for analysis.ResultsThere was a potential association between hypertension, primarily in systolic blood pressure, and an elevated epilepsy risk, while the relationship between hypertension in diastolic blood pressure and epilepsy risk remained inconclusive. Sensitivity analyses suggest an absence of substantial heterogeneity and confounding effects, suggesting the reliability of our findings.ConclusionsOur study lays the groundwork for further investigations into the mechanisms of this causal relationship, which may potentially involve vascular change, neuroinflammatory pathways, and alterations in cerebral blood flow, which are crucial for understanding the complex hypertension-epilepsy nexus.