Lack of causal association between epilepsy and dementia: A Mendelian randomization analysis.

OBJECTIVE: Epidemiological studies have reported an association between epilepsy and dementia. However, the causal relationship between epilepsy and the risk of dementia is not clear. We aimed to inspect the causal effect of epilepsy on memory loss and dementia. METHODS: We analyzed summary data of epilepsy, memory loss, and dementia from the genome-wide association study (GWAS) using the two-sample Mendelian randomization (MR) method. We used the estimated odds ratio of memory loss and dementia associated with each of the genetically defined traits to infer evidence for a causal relationship with the following exposures: all epilepsy, focal epilepsy (including focal epilepsy with hippocampal sclerosis, lesion-negative focal epilepsy, and focal epilepsy with other lesions), and genetic generalized epilepsy (including childhood absence epilepsy, generalized tonic-clonic seizures alone, Juvenile absence epilepsy, and Juvenile myoclonic epilepsy). RESULTS: According to the result of MR using the inverse variance weighted method (IVW), we found that genetically predicted epilepsy did not causally increase the risk of memory loss and dementia (p > 0.05). Results of the MR-Egger and weighted median method were consistent with the IVW method. CONCLUSIONS: No evidence has been found to support the notion that epilepsy can result in memory loss and dementia. The associations observed in epidemiological studies could be attributed, in part, to confounding or nongenetic determinants.

Treatment with a flow diverter-assisted coil embolization for ruptured blood blister-like aneurysms of the internal carotid artery: a technical note and analysis of single-center experience with pooled data.

Treatment of blood blister-like aneurysms (BBAs) of the supraclinoid internal carotid artery (ICA) with flow diverters (FDs) has become widespread in recent years. However, ruptured blood blister-like aneurysm (BBA) of ICA treatment with flow diverter-assisted coil embolization (FDAC) remains controversial. Moreover, limited direct comparative studies have been conducted between the two treatment modalities, FDs and FDAC, for BBAs. The purpose of this study was to document our experience and evaluate the effectiveness and safety of FDAC. We conducted a retrospective analysis of clinical and radiological information from ten patients who experienced ruptured BBAs of the supraclinoid ICA at our center from January 2021 to February 2023. The technical details of FDAC for ruptured BBAs were described, and the technical steps were named "pipeline embolization device (PED)-Individualized shaping(microcatheter)-Semi deploying-Rivet(coils)-Massage(microwire)" as the PEISSERM technique. Clinical outcomes were assessed using the modified Rankin Scale (mRS), whereas radiological results were determined through angiography. A pooled analysis was implemented, incorporating data from literature sources that reported perioperative and long-term clinical and angiographic outcomes of ruptured BBAs treated with FD and FDAC strategies, along with our data. Data in our analysis pool were categorized into FD and FDAC strategy groups to explore the preferred treatment modalities for BBAs. The PEISSERM technique was utilized to treat ten patients, seven males, and three females, with an average age of 41.7 years. A single PED was deployed in conjunction with coils in all ten patients. All PEDs were documented to have good wall apposition. The immediate postoperative angiograms demonstrated Raymond grade I in ten aneurysms. Angiographic follow-up of nine patients at 4-25 months showed total occlusion of the aneurysms. At the most recent follow-up, the mRS scores of nine patients hinted at a good prognosis. Pooled analysis of 233 ICA-BBA cases of FD revealed a technical success rate of 91% [95% confidence interval (CI), 0.88 to 0.95], a rate of complete occlusion of 79% (95% CI, 0.73 to 0.84), a recurrence rate of 2% (95% CI, 0.00 to 0.04), a rebleed rate of 2% (95% CI, 0.00 to 0.04), and the perioperative stroke rate was 8% (95% CI, 0.04 to 0.11). The perioperative mortality was 4% (95% CI, 0.01 to 0.07). The long-term good clinical outcome rate was 85% (95% CI, 0.80 to 0.90). The mortality rate was 6% (95% CI, 0.03 to 0.09). Results from the subgroup analysis illustrated that the FDAC strategy for BBAs had a significantly higher immediate postoperative complete occlusion rate (P < 0.001), total occlusion rate (P = 0.016), and a good outcome rate (P = 0.041) compared with the FD strategy. The FDAC strategy can yield a higher rate of good outcomes than the FD strategy. The PEISSERM technique employed by the FDAC is a reliable and effective treatment approach as it can minimize the hemodynamic burden of BBA's fragile dome, thereby achieving an excellent occlusion rate. The PEISSERM technique in the FDAC strategy contributes to understanding the BBA's treatment and offers a potentially optimal treatment for BBA.

Circulating Biomarkers and Risk of Hypertension: A Two-Sample Mendelian Randomisation Study.

OBJECTIVE: This study systematically assessed circulating proteins to identify new serum biomarkers and risk of hypertension using Mendelian randomisation. METHODS: The associations between 4,782 human circulating proteins and the risk of hypertension were evaluated using two-sample Mendelian randomisation. The FinnGen study demonstrated a link between genetic predisposition and hypertension in 85,438 cases and 223,663 controls. RESULTS: Inverse variance weighted and sensitivity analysis revealed nine proteins in circulation that have a causative effect on hypertension. SMOC1 and TIE1 were determined to be causative factors in the decreased likelihood of developing hypertension, with odds ratios of 0.86 (95% CI 0.81-0.91; p=1.06e-06) and 0.96 (95% CI 0.94-0.98; p=9.39e-05), respectively. NDUFB4, ETHE1, POFUT2, TRIL, ADAM23, GXYLT1, OXT, TPST2, and TMCC3 showed a possible connection to hypertension. CONCLUSIONS: This two-sample Mendelian randomisation study found that SMOC1 and TIE1 are causally linked to hypertension, making them a promising target for therapy.

Structure and function of corticospinal projection originating from supplementary motor area.

PURPOSE: The importance of supplementary motor area (SMA) for motor function and compensation for primary motor area (M1) has received increased attention. METHODS: We used diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS) to evaluate structure and function of corticospinal projection originating from SMA. Fibers of corticospinal projection originating from M1 (CST) and SMA (ACST) were analyzed. ACST originating from mesial SMA area formed separate white matter bundles leaving the anterior part of M1 area, which then entered the posterior limb of the internal capsule. Projection and overlap of both CST and ACST were detected on medulla. RESULTS: Fibers of contralesional ACST were more than that of ipsilesional ACST in patients with SMA tumors (p<0.05). In patients with SMA tumor, all patients experienced temporary akinesia postoperatively. Seven hundred forty-one fibers of ipsilateral ACST and no fibers of ipsilateral CST were detected in the patient with M1 glioma, while most of contralateral limb movement was preserved. MEP could be evoked by stimulating SMA area as well as M1 area. ACST originated from SMA area and projected to the medial medulla. CONCLUSION: SMA area and ACST integrity contributed to contralateral motor function and were a compensation for M1 lesion and damaged CST.

Lower Serum Iron and Hemoglobin Levels are Associated with Acute Seizures in Patients with Ruptured Cerebral Aneurysms.

BACKGROUND AND OBJECTIVE: The aim of the study is to investigate the value of serum iron and hemoglobin levels for predicting acute seizures following aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Clinical and laboratorial data from patients with ruptured intracranial aneurysms were collected in the retrospective study. Age, sex, symptom onset, history of diabetes and hypertension, history of coronary artery disease, temperature, Hunt-Hess grade, Fisher grade, aneurysm location, hemoglobin, serum potassium, sodium, calcium, phosphorus, and iron were collected. Acute seizures were determined as seizures within 1 week following aSAH. Propensity score matching (PSM) analyses were performed to correct imbalances in patient characteristics between seizure and non-seizure groups. RESULTS: A total of 760 patients were included. Incidence of acute seizures following aSAH was 6.4%. In the univariate analysis, significant differences were detected in age, admission Hunt-Hess grade, Fisher grade, hemoglobin, serum sodium, and serum iron between seizure and non-seizure groups. In multivariate logistic regression model, lower serum iron was considered as a risk factor for acute seizures (OR 0.182, 95% CI 0.084-0.393, p = 0.000), as well as lower hemoglobin (OR 0.977, 95% CI 0.962-0.993, p = 0.004) and higher serum sodium (OR 1.072, 95% CI 1.003-1.145, p = 0.039). After PSM, there were no significant differences in age, admission Hunt-Hess grade, Fisher grade, and serum sodium between seizure and non-seizure groups. The matched seizure group had lower serum iron and hemoglobin levels compared with the matched non-seizure group (p < 0.05). The optimal cutoff value for serum iron and hemoglobin levels as a predictor of acute seizure after aSAH was determined as 9.9 mmol/L (sensitivity was 81.63% and the specificity was 65.40%) and 119 g/L (sensitivity was 63.27% and the specificity was 70.18%), respectively. CONCLUSIONS: Serum iron and hemoglobin levels were inversely associated with a high risk of acute seizures following aSAH.

Glutamate/glutamine metabolism coupling between astrocytes and glioma cells: neuroprotection and inhibition of glioma growth.

Glioma glutamate release has been shown to promote the growth of glioma cells and induce neuronal injuries from epilepsy to neuronal death. However, potential counteractions from normal astrocytes against glioma glutamate release have not been fully evaluated. In this study, we investigated the glutamate/glutamine cycling between glioma cells and astrocytes and their impact on neuronal function. Co-cultures of glioma cells with astrocytes (CGA) in direct contact were established under different mix ratio of astrocyte/glioma. Culture medium conditioned in these CGAs were sampled for HPLC measurement, for neuronal ratiometric calcium imaging, and for neuronal survival assay. We found: (1) High levels of glutaminase expression in glioma cells, but not in astrocytes, glutaminase enables glioma cells to release large amount of glutamate in the presence of glutamine. (2) Glutamate levels in CGAs were directly determined by the astrocyte/glioma ratios, indicating a balance between glioma glutamate release and astrocyte glutamate uptake. (3) Culture media from CGAs of higher glioma/astrocyte ratios induced stronger neuronal Ca(2+) response and more severe neuronal death. (4) Co-culturing with astrocytes significantly reduced the growth rate of glioma cells. These results indicate that normal astrocytes in the brain play pivotal roles in glioma growth inhibition and in reducing neuronal injuries from glioma glutamate release. However, as tumor growth, the protective role of astrocytes gradually succumb to glioma cells.

Selection of DNA aptamers against epidermal growth factor receptor with high affinity and specificity.

Epidermal growth factor receptor (EGFR/HER1/c-ErbB1), is overexpressed in many solid cancers, such as epidermoid carcinomas, malignant gliomas, etc. EGFR plays roles in proliferation, invasion, angiogenesis and metastasis of malignant cancer cells and is the ideal antigen for clinical applications in cancer detection, imaging and therapy. Aptamers, the output of the systematic evolution of ligands by exponential enrichment (SELEX), are DNA/RNA oligonucleotides which can bind protein and other substances with specificity. RNA aptamers are undesirable due to their instability and high cost of production. Conversely, DNA aptamers have aroused researcher's attention because they are easily synthesized, stable, selective, have high binding affinity and are cost-effective to produce. In this study, we have successfully identified DNA aptamers with high binding affinity and selectivity to EGFR. The aptamer named TuTu22 with Kd 56±7.3nM was chosen from the identified DNA aptamers for further study. Flow cytometry analysis results indicated that the TuTu22 aptamer was able to specifically recognize a variety of cancer cells expressing EGFR but did not bind to the EGFR-negative cells. With all of the aforementioned advantages, the DNA aptamers reported here against cancer biomarker EGFR will facilitate the development of novel targeted cancer detection, imaging and therapy.

Association of dietary fiber intake with epileptic seizures in U.S. adults: A Population-base study of 13,277 participants.

OBJECTIVE: Epilepsy, a neurological disorder, is identified by the presence of recurrent seizures. We aimed to detect dietary fiber intake and its association with epilepsy prevalence in U.S. adults. METHODS: This cross-sectional study obtained data from the 2013-2018 National Health and Nutrition Examination Survey database. Univariate and multivariate logistic regression models were employed to estimate the association between dietary fiber intake and epilepsy prevalence. The restricted cubic spline (RCS) model was also applied to investigate the dose-response relationships between dietary fiber intake and epileptic seizure events(ESEs). RESULTS: Our final sample included 13,277 NHANES participants, with the average prevalence of ESEs being 1.09 % (145/13277). After adjusting for all confounding factors, the third quartile of dietary fiber intake levels remained significantly associated with a decreased risk of ESEs[odds ratios (OR) 0.54,95 % confidence interval (CI) 0.33-0.88, P = 0.014)] compared to the first quartile. Higher fiber intake indicated a stable negative association with ESEs in the multivariate logistic regression analysis, weighted generalized additive model. A nonlinear dose-response relationship was observed between dietary fiber intake levels and decreased ESEs risk (P for overall=0.017, P for nonlinear=0.155). Interaction tests showed no significant effect of demographic and disease status on the association between dietary fiber intake and ESEs. CONCLUSION: In this cross-sectional study, people with a high dietary fiber intake were at a reduced risk of ESEs. However, further prospective studies are needed to investigate the effect of dietary fiber intake in epilepsy events and to determine causality.