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Aims: Previous studies suggest potential associations between epilepsy, anti‐epileptic drugs (AEDs), and levels of vitamin D and vitamin D‐binding protein (VDBP). This study aims to investigate the causal relationships among these variables using Mendelian Randomization (MR) methods. Methods: Using summary data from genome‐wide association studies on serum 25‐hydroxyvitamin D [25(OH)D] levels (N = 417,580), VDBP concentrations (N = 65,589), and various types of epilepsy (Ncases = 27,559), MR analyses were conducted to determine bidirectional causal relationships among these variables. Additionally, eQTL data from eQTLGen (N = 31,684) were employed to model the effects of AEDs and evaluate their causal impact on both biomarkers. Results: No causal relationships were found between serum 25(OH)D or VDBP levels and epilepsy. Although genetically predicted focal epilepsy risk was potentially associated with increased serum 25(OH)D levels (OR 1.031, 95% CI: 1.006–1.058, p = 0.017), and a higher genetic risk of juvenile myoclonic epilepsy was linked to lower VDBP levels (OR 0.977, 95% CI: 0.961–0.993, p = 0.004), both associations lost significance after multiple correction. Furthermore, significant associations were observed between serum 25(OH)D levels and AED target genes SCN4A, GABBR1, CA13, ALDH5A1, and CA8. No significant associations were found between AED target genes and VDBP levels after correction. Conclusion: No causal relationships were found between genetically determined serum 25(OH)D levels, VDBP, and epilepsy or its subtypes. Furthermore, the use of AEDs, such as Carbamazepine, Oxcarbazepine, Progabide, and Valproic Acid, reduces serum 25(OH)D levels, while not affect VDBP levels. [ABSTRACT FROM AUTHOR]

Purpose: Sturge-Weber syndrome (SWS), a rare congenital neurological and skin disorder, is frequently associated with drug-resistant epilepsy. Translocation of high mobility group box 1 (HMGB1) protein from the nucleus to the cytoplasm or extracellular milieu has been implicated in neuroinflammatory processes contributing to the development of epileptogenesis. This study aimed to explore the expression and distribution of HMGB1 in brain tissue from SWS patients with drug-resistant epilepsy, with the goal of elucidating its potential involvement in the pathogenesis of epilepsy. Patients and Methods: The study enrolled eight patients with drug-resistant epilepsy who underwent hemispherectomy. Brain tissue specimens were obtained and analyzed using immunofluorescence staining to detect HMGB1 distribution in microglia, astrocytes, or different neuronal subtypes. Correlation analyses were performed to investigate the potential relationship between HMGB1 translocation within cells and the clinical characteristics of SWS patients. Results: In lesional tissues of SWS patients, we observed significantly higher cytoplasmic HMGB1 levels. Meanwhile, HMGB1 was widely distributed in the cytoplasm of microglia and neurons, while in astrocytes, it was primarily localized in the nucleus. This translocation occurred across many neuronal subtypes, including excitatory glutamatergic, inhibitory GABAergic, and cholinergic neurons. The lower proportion of HMGB1-translocated cholinergic neurons was seen compared to the other two neuronal subtypes. Furthermore, no correlation was found between cytoplasmic HMGB1 levels and clinical characteristics of SWS patients. Conclusion: The results suggest the involvement of HMGB1 in the pathogenesis of drug-resistant epilepsy in SWS patients. Additional research is required to elucidate the precise mechanisms and potential therapeutic targets associated with HMGB1 that underlie the epilepsy linked to SWS. [ABSTRACT FROM AUTHOR]

Objective To investigate the transcriptomic characteristics of the brain tissue in patients with Rasmussen encephalitis (RE). Methods RNA-seq technique was used to detect the gene expression profiles in the brain tissues from 4 patients with RE and 4 with temporal lobe epilepsy (TLE) admitted to Sanbo Brain Hospital, Capital Medical University between April, 2008 and December, 2013. Results Cluster analysis showed significant differences in the differentially expressed genes (DEGs) in the brain tissue between the patients with RE and those with TLE. We identified a total of 1 285 DEGs, of which 782 (60.9%) were down-regulated and 503 (39.1%) were up-regulated in RE. The up-regulated DEGs were mainly enriched in the pathways associated with neuronal signal transduction, possibly in relation with frequent seizures in patients with RE; the down-regulated DEGs were mainly enriched in the pathways associated with cytoskeleton, cell cycle and chemotaxis, which may be related to neuronal loss and regeneration and immune responses to infection by some pathogens in the brain tissue of patients with RE. TAS2R40, HTR4 and NAP1L2 were identified as the key up-regulated DEGs, and CXXC1, SEPTIN8 and CCR7 as the key down-regulated DEGs. Conclusion The brain tissue of patients with RE shows characteristic transcriptomic changes, and the DEGs are mainly enriched in neuronal signal transduction, cell cycle and chemotaxis-related pathways.

Objectives We aimed to investigate the clinicopathologic features of and genetic changes in Sturge-Weber syndrome (SWS) in patients with refractory epilepsy. Methods Clinical data were retrospectively analyzed. H&E and immunohistochemistry were performed to assess pathologic changes. Targeted amplicon sequencing was applied to investigate the somatic GNAQ (c.548G>A) mutation. The potential predictors of seizure outcomes were estimated by univariate and multivariate statistical analyses. Results Forty-eight patients with SWS and refractory epilepsy were enrolled. According to the imaging data and pathologic examination, ipsilateral hippocampal sclerosis (HS), calcification of leptomeningeal arteries, and focal cortical dysplasia were found in 14 (29.2%), 31 (64.6%), and 37 (77.1%) patients, respectively. A high frequency of GNAQ alteration was detected in both cerebral cortex (57.7%) and ipsilateral hippocampus (50.0%) from patients with SWS. During follow-up, 43 of 48 patients (85.4%) had achieved seizure control (Engel class I). Statistically, HS signs on imaging were found to be independent predictors of unfavorable seizure outcomes (P =.015). Conclusions Calcification of leptomeningeal arteries, focal cortical dysplasia, and GNAQ alteration are common features in SWS pathology. Patients with refractory epilepsy caused by SWS can achieve satisfactory seizure control after surgery, but seizure control was compromised in patients with comorbid HS. [ABSTRACT FROM AUTHOR]