Objective: With detailed studies of ATP1A3-related diseases, the phenotypic spectrum of ATP1A3 has greatly expanded. This study aimed to potentially identify the mechanisms by which ATP1A3 caused neurological dysfunction by analyzing the clinical features and phenotypes of ATP1A3-related diseases, and exploring the distribution patterns of mutations in the subregions of the ATP1A3 protein, thus providing new and effective therapeutic approaches.Methods: Databases of PubMed, Online Mendelian Inheritance in Man, and Human Gene Mutation Database, Wanfang Data, and Embase were searched for case reports of ATP1A3-related diseases. Following case screening, we collected clinical information and genetic testing results of patients, and analyzed the disease characteristics on the clinical phenotype spectrum associated with mutations, genetic characteristics of mutations, and effects of drug therapy.Results: We collected 902 clinical cases related to ATP1A3 gene. From the results of previous studies, we further clarified the clinical characteristics of ATP1A3-related diseases, such as alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism; cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss syndrome, and relapsing encephalopathy with cerebellar ataxia, frequency of mutations in different phenotypes and their distribution in gene and protein structures, and differences in mutations in different clinical phenotypes. Regarding the efficacy of drug treatment, 80 of the 124 patients with AHC were treated with flunarizine, with an effectiveness rate of ~64.5%.Conclusions: Nervous system dysfunction due to mutations of ATP1A3 gene was characterized by a group of genotypic–phenotypic interrelated disease pedigrees with multiple clinical manifestations. The presented results might help guide the diagnosis and treatment of ATP1A3-related diseases and provided new ideas for further exploring the mechanisms of nervous system diseases due to ATP1A3 mutations.

Background: Autophagy plays essential roles in the development and pathogenesis of mesial temporal lobe epilepsy (mTLE). In this research, we aim to identify and validate the autophagy-related genes associated with mTLE through bioinformatics analysis and experimental validations. Methods: We obtained the dataset GSE143272 and high-throughput sequencing results of mTLE from public databases. Potential differentially expressed autophagy-related genes related to mTLE were identified using R software. Subsequently, genomes pathway enrichment analysis, protein-protein interactions (PPIs), and the gene ontology (GO) enrichment were performed for the selected autophagy-related genes. The mRNA expression profiles of hub genes were then used to establish a least absolute shrinkage and selection operator (LASSO) model. Finally, seven hub candidate autophagy-related genes were confirmed in hippocampus using the lithium-pilocarpine chronic epilepsy model. Results: A total of 40 differential expression genes (DEGs) among the core autophagy-related genes were identified. The analysis results of PPI revealed that interactions among these DEGs. KEGG pathway and GO analysis of selected candidate autophagy-related genes indicated that those enriched terms mainly focused on macroautophagy, regulation of autophagy, cellular response to extracellular stimulus and mitochondrion disassembly. The results suggested that SQSTM1, VEGFA, BNIP and WIPI2 were consistent with the bioinformatics analysis. The expression levels of SQSTM1 and VEGFA in epilepsy model samples were significantly higher than those in normal control, while BNIP and WIPI2 expression levels were notably decreased. The final hub gene-based LASSO regression model accurately predicted the occurrence of epilepsy (AUC = 0.88). Conclusions: Through bioinformatics analysis of public data, we identified 40 candidate autophagy-related genes associated with mTLE. SQSTM1, VEGFA, BNIP and WIPI2 may play significant roles in autophagy, influencing the onset and development of mTLE by regulating autophagy pathway. These findings deepen our understanding of mTLE, and may serve as sensitive and valuable indicators for the prognosis and diagnosis of this condition.

Objective: This study evaluated the efficacy and safety of adjunctive clobazam (CLB) in Chinese patients with drug-resistant epilepsy (DRE). Methods: We retrospectively included 121 DRE patients receiving adjunctive CLB at the Epilepsy Center of the Seventh Affiliated Hospital of Sun Yat-sen University (Jan 2023-May 2025). Patients were followed at 1, 3, 6, 9, and 12 months or longer. Data collected included epilepsy etiology, seizure type, frequency, treatment duration, dosage, and adverse events. Response was defined as ≥50% reduction in seizure frequency from baseline. Results: A total of 121 patients were included (age at medication use 32.4 ± 13.5 years; mean three prior failed antiseizure medications; mean follow-up 12 months). Seizure types were focal (18.2%), generalized (7.4%), and both (74.4%). At first follow-up, 51.2% achieved ≥50% seizure reduction and 39.7% were seizure freedom; at last follow-up, 85.9% responded and 51.6% were seizure freedom. Response rates increased over time (all p < 0.001). Adults had higher response ( p = 0.046) and seizure freedom rates ( p = 0.041) than children. Concomitant oxcarbazepine (OXC) was associated with increased seizure freedom ( p = 0.03), whereas valproate (VPA) was associated with low response rate ( p = 0.013) but not with seizure freedom. Age at medication (OR = 1.032, p = 0.035), CLB dosage (OR = 1.093, p = 0.004), and OXC co-therapy (OR = 2.311, p = 0.04) were independent predictors of seizure freedom. Most common adverse events were somnolence/mental fatigue (9.9%) and hypersomnia (5%). Conclusion: Adjunctive CLB significantly reduced seizures in DRE with sustained efficacy. Higher dosage, longer treatment duration, and concomitant OXC use were associated with improved outcomes. CLB showed favorable efficacy, wide applicability, and acceptable safety.

Focal cortical dysplasia (FCD) is a predominant cause of drug-resistant epilepsy in children, yet the neuro-immune mechanisms underlying this condition are