EEG microstates in epilepsy with and without cognitive dysfunction: Alteration in intrinsic brain activity.

OBJECTIVE: This study aims to investigate the difference between epilepsy comorbid with and without cognitive dysfunction. METHOD: Participants were classified into patients with epilepsy comorbid cognitive dysfunction (PCCD) and patients with epilepsy without comorbid cognitive dysfunction (nPCCD). Microstate analysis was applied based on 20-channel electroencephalography (EEG) to detect the dynamic changes in the whole brain. The coverage, occurrence per second, duration, and transition probability were calculated. RESULT: The occurrence per second and the coverage of microstate B in the PCCD group were higher than that of the nPCCD group. Coverage in microstate D was lower in the PCCD group than in the nPCCD group. In addition, the PCCD group has a higher probability of A to B and B to A transitions and a lower probability of A to D and D to A transitions. CONCLUSION: Our research scrutinizes the disparities observed within EEG microstates among epilepsy patients both with and without comorbid cognitive dysfunction. SIGNIFICANCE: EEG microstate analysis offers a novel metric for assessing neuropsychiatric disorders and supplies evidence for investigating the mechanisms and the dynamic change of epilepsy comorbid cognitive dysfunction.

COVID-19 vaccination for patients with epilepsy: A Chinese expert consensus.

Coronavirus disease-2019 (COVID-19) first emerged in late 2019 and has since spread worldwide. More than 600 million people have been diagnosed with COVID-19, and over 6 million have died. Vaccination against COVID-19 is one of the best ways to protect humans. Epilepsy is a common disease, and there are approximately 10 million patients with epilepsy (PWE) in China. However, China has listed "uncontrolled epilepsy" as a contraindication for COVID-19 vaccination, which makes many PWE reluctant to get COVID-19 vaccination, greatly affecting the health of these patients in the COVID-19 epidemic. However, recent clinical practice has shown that although a small percentage of PWE may experience an increased frequency of seizures after COVID-19 vaccination, the benefits of COVID-19 vaccination for PWE far outweigh the risks, suggesting that COVID-19 vaccination is safe and recommended for PWE. Nonetheless, vaccination strategies vary for different PWE, and this consensus provides specific recommendations for PWE to be vaccinated against COVID-19.

The Role of 5-HTR6 in Mossy Fiber Sprouting: Activating Fyn and p-ERK1/2 in Pilocarpine-Induced Chronic Epileptic Rats.

OBJECTIVE: Our primary objective is to verify whether 5-HTR6 is involved in the development of mossy fiber sprouting (MFS), and to determine how the progression of MFS is affected by 5-HTR6. METHODS: A total of 90 male adult Sprague-Dawley rats were allocated into either the control group (n=36) or the epileptic group (n=54). Status epilepticus (SE) of rats was induced by the intraperitoneal (i.p.) injection of LiCl-pilocarpine. We conducted our experiments in two stages. The first stage involves equally dividing 36 epileptic rats into three groups with treatments of none, 5-HTR6 antagonist SB-27104 (SB) and vehicle DMSO. Then behavior and electroencephalogram (EEG) of rats were monitored by video-EEG. The second stage involves dividing 126 epileptic rats into seven groups with treatments of none, 10% DMSO, SB (100 µg/kg), Fyn antagonist PP2 (50 µg/kg), p-ERK1/2 antagonist PD-98059 (30 µg/kg), SB (100 µg/ kg) + PP2 (50 µg/kg); SB (100 µg/kg) + PD-98059 (30 µg/kg). We also treated 18 rats in the control group of the first stage with 100 µg/kg 5-HTR6 agonist WAY-181187 (WAY). MFS of rats was detected through the approach of Timm's staining. Finally, expressions of 5-HTR6, Fyn, p-ERK1/2 and GAP-3 were qualified and semi-quantified via western blotting or RT-PCR. RESULTS: Induction of SE could stimulate formation of MFS and increased GAP-43 expressions. Expressions of 5-HTR6, Fyn and p-ERK1/2 were also up-regulated with increasing time after establishment of SE models. The development of MFS was remarkably inhibited by SB, PP2 and PD. Compared to the single antagonist, such an inhibitory effect was enhanced by SB+PD or SB+PP. Moreover, treatment of healthy rats with WAY would contribute to up-regulated Fyn and p-ERK1/2 expressions, as well as development of MFS (P < 0.05). Suppression of Fyn triggered a down-regulating trend of p-ERK1/2 (P < 0.05), however, suppressed p-ERK1/2 did not have such a significant effect on Fyn expression. CONCLUSION: HTR6 may affect the progression of MFS by activating both p-ERK1/2 and Fyn, which further modulate the expression of GAP-43.

Genetic epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis.

BACKGROUND: Genetic studies have shown that C9orf72, SOD1, TARDBP and FUS are the most common mutated genes in amyotrophic lateral sclerosis (ALS). Here, we performed a meta-analysis to determine the mutation frequencies of these major ALS-related genes in patients with ALS. METHODS: We performed an extensive literature research to identify all original articles reporting frequencies of C9orf72, SOD1, TARDBP and FUS mutations in ALS. The mutation frequency and effect size of each study were combined. Possible sources of heterogeneity across studies were determined by meta-regression, sensitivity analysis and subgroup analysis. RESULTS: 111 studies were included in the meta-analysis. The overall pooled mutation frequencies of these major ALS-related genes were 47.7% in familial amyotrophic lateral sclerosis (FALS) and 5.2% in sporadic ALS (SALS). A significant difference was identified regarding the frequencies of mutations in major ALS genes between European and Asian patients. In European populations, the most common mutations were the C9orf72 repeat expansions (FALS 33.7%, SALS 5.1%), followed by SOD1 (FALS 14.8%, SALS 1.2%), TARDBP (FALS 4.2%, SALS 0.8%) and FUS mutations (FALS 2.8%, SALS 0.3%), while in Asian populations the most common mutations were SOD1 mutations (FALS 30.0%, SALS 1.5%), followed by FUS (FALS 6.4%, SALS 0.9%), C9orf72 (FALS 2.3%, SALS 0.3%) and TARDBP (FALS 1.5%, SALS 0.2%) mutations. CONCLUSIONS: These findings demonstrated that the genetic architecture of ALS in Asian populations is distinct from that in European populations, which need to be given appropriate consideration when performing genetic testing of patients with ALS.

[Predictors of internal borderzone infarcts in atherosclerotic middle cerebral artery stenosis].

OBJECTIVE: To explore the independent predictors of internal borderzone (IBZ) infarcts in patients with atherosclerotic middle cerebral artery stenosis/occlusion (MCAS). METHODS: A total of 167 hospitalized patients with atherosclerotic MCAS during January 2008 and March 2014 were retrospectively analyzed. They were divided into "with IBZ group" (n = 55) and "without IBZ group" (n = 112) according to the findings of magnetic resonance images (MRI). Their clinical data were collected including demographics, traditional vascular risk factors, stenotic degree of MCA and other cerebral supply arteries, TICI grading for antegrade blood flow, ASITN/SIR grading for collateral circulation and other variables. The intra-group data were compared by univariate analysis. Variables with P < 0.1 were included into multivariate Logistic regression model for obtaining the independent predictors of IBZ. Two models were established including either TICI-grading or stenotic degree of MCAS due to close correlations between two variables. RESULTS: There were 45 females and 122 males with a mean age of 54 ± 12 years. Variables with a P value <0.1 in univariate analysis included relatively low blood pressure (P = 0.006), stenotic degree of MCAS (P = 0.012), TICI-grading (P = 0.003), history of hypertension (P = 0.055) and ASITN-grading (P = 0.067). In multivariate model I, independent predictors of IBZ included TICI-grading (OR 4.310, 95%CI 1.698-10.869, P = 0.002), history of hypertension (OR 0.458, 95%CI 0.224-0.936, P = 0.032), relatively low blood pressure (OR 3.848; 95%CI 1.345-7.983, P = 0.039). In multivariate model II, independent predictors of IBZ included stenotic degree of MCAS (P = 0.006; severe vs moderate: OR 4.796, 95%CI 1.676-13.729, P = 0.003; occlusion vs moderate: OR 5.537, 95%CI 1.846-16.603, P = 0.002). The two models had a similar area under the curve (AUC) of receiver operating curve (ROC) of 0.702 (95%CI 0.618~0.787, P < 0.001) and 0.709 (95%CI 0.626-0.792, P < 0.001). CONCLUSION: Severe stenosis or total occlusion of MCA, impairment of antegrade blood flow and relatively low blood pressure are the independent risk factors of IBZ. And history of hypertension is a protective fact or of IBZ in patients with MCAS.

[Changes of left ventricular remodeling in hypertension patients with carotid atherosclerosis of phlegm-dampness syndrome].

OBJECTIVE: To study changes of left ventricular remodeling (LVR) in hypertension patients with carotid atherosclerosis (CAS) of phlegm-dampness syndrome (PDS). METHODS: Doppler ultrasonography data of CAS were observed in 223 hypertension patients with CAS (as the hypertension group, including 119 patients of the PDS group and 104 of the non-PDS group), 81 CAS patients with non-hypertension, and 19 non-hypertension non-CAS patients (as the control group). The difference in the degree of LVR was compared among the above groups. RESULTS: The left ventricular posterior wall thickness (LVPWT), inter ventricular septum thickness (IVS), E/A were higher in the hypertension group than in the non-hypertension group (P < 0.05). The left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic diameter (LVESD), stroke volume (SV) were higher in the soft plaque hypertension group and the soft plaque non-hypertension group than in the hard plaque group, the thickening intimal group, and the normal intimal group (P < 0.01 , P < 0.05). The LVEDD, LVESD, and SV were higher, and the ejection fraction (EF) was lower in the PDS hypertension group than in the non-PDS hypertension group (all P < 0.05). Of them, LVEDD, LVESD, and SV were higher in the soft plaque group than in the hard plaque group (P < 0.01), the thickening intimal group (P < 0.01) and the normal intimal group (P < 0.05). There was no statistical difference in PDS hypertension between the soft plaque group and the hard plaque group (P > 0.05). CONCLUSION: The hypertension patients with CAS of PDS might be correlated to LVR, and LVR was more obviously in the soft plaque patients.

Intrinsic brain activity differences in perampanel-responsive and non-responsive drug-resistant epilepsy patients: an EEG microstate analysis.

Background: Drug-resistant epilepsy (DRE) patients exhibit aberrant large-scale brain networks. Perampanel may be a therapeutic option for controlling seizures in these patients. Objective: We aim to explore the differences of resting-state electroencephalogram (EEG) microstate in perampanel-responsive and non-responsive DRE patients. Design: Retrospective study. Methods: Clinical data were collected from DRE patients who received perampanel treatment at the Fujian Medical University Union Hospital from June 2020 to September 2021, with a minimum follow-up of 6 months. Patients were classified into three groups based on the extent of reduction in seizure frequency: non-responsive (seizure reduction <50%), responsive (seizure reduction >50% but not seizure-free), and seizure-free. Resting-state EEG data sets of all participants were subjected to EEG microstate analysis. The study comprehensively compared the mean duration, frequency per second, and temporal coverage of each microstate among the three groups. Results: A total of 76 perampanel-treated DRE patients were categorized into three groups based on their response to treatment: non-responsive (n = 20), responsive (n = 36), and seizure-free (n = 20), according to the degree of seizure frequency reduction. The results of EEG microstate analysis revealed no statistically significant distinctions in frequency, duration, and coverage of microstate D in these DRE patients. However, the seizure-free group showed significantly increased duration and coverage of microstate A, frequency and coverage of microstate B, and significantly decreased duration, frequency, and coverage of microstate C when compared with the other groups. Conclusion: Microstate A, B, and D is associated with the sensorimotor network, visual network, salience network, and attention network, respectively. This study demonstrates statistically significant differences in the sensorimotor, visual, and salience networks, but not in the attention network, between perampanel-responsive and non-responsive DRE patients.

ADCY3: the pivotal gene in classical ketogenic diet for the treatment of epilepsy.

Objective: Epilepsy is a common neurological disorder characterized by recurrent epilepsy episodes. As a non-pharmacological treatment, the ketogenic diet has been widely applied in treating epilepsy. However, the exact therapeutic mechanism of the ketogenic diet for epilepsy remains unclear. This study investigates the molecular mechanisms of the ketogenic diet in regulating fatty acid metabolism and activating the ADCY3-initiated cAMP signaling pathway to enhance neuronal inhibition and thereby treat epilepsy. Methods and results: Meta-analysis reveals that the ketogenic diet is superior to the conventional diet in treating epilepsy. Animal experiments demonstrate that the ketogenic diet is more effective than the conventional diet in treating epilepsy, with the best results achieved using the classic ketogenic diet. Transcriptome sequencing analysis identifies six essential genes, among which ADCY3 shows increased expression in the ketogenic diet. In vivo experiments confirm that the activation of the cAMP-PKA signaling pathway by ADCY3 enhances neuronal inhibition and improves epilepsy control. Conclusion: Clinical observations indicate that the ketogenic diet improves patient epilepsy episodes by regulating the ADCY3-initiated cAMP signaling pathway.

Pharmacological inhibition of S6K1 rescues synaptic deficits and attenuates seizures and depression in chronic epileptic rats.

BACKGROUND: Recent studies have shown that mTOR signaling plays an important role in synaptic plasticity. However, the function of S6K1, the mechanistic target of rapamycin kinase complex 1 (mTORC1) substrate, in epilepsy remains unknown. AIMS: Our present study aimed to explore the mechanism by which S6K1 is involved in chronic epilepsy. METHODS: First, immunostaining was used to measure neurite length and complexity in kainic acid (KA)-treated primary cultured neurons treated with PF-4708671, a highly selective S6K1 inhibitor. We obtained evidence for the role of S6K1 in protecting and promoting neuronal growth and development in vitro. Next, to explore the function and mechanism of the S6K1 inhibitor in epilepsy, a pilocarpine-induced chronic epileptic rat model was established. In vivo electrophysiology (including local field potentiation in CA1 and long-term potentiation), depression/anxiety-like behavior tests, and Golgi staining were performed to assess seizure behavior, power spectral density, depression/anxiety-like behavior, and synaptic plasticity. Furthermore, western blotting was applied to explore the potential molecular mechanisms. RESULTS: We found that inhibition of S6K1 expression significantly decreased seizures and depression-like behavior and restored power at low frequencies (1-80 Hz), especially in the delta, theta, and alpha bands, in chronic epileptic rats. In addition, PF-4708671 reversed the LTP defect in hippocampal CA3-CA1 and corrected spine loss and dendritic pathology. CONCLUSION: In conclusion, our data suggest that inhibition of S6K1 attenuates seizures and depression in chronic epileptic rats via the rescue of synaptic structural and functional deficits. Given the wide range of physiological functions of mTOR, inhibition of its effective but relatively simple functional downstream molecules is a promising target for the development of drugs for epilepsy.

Role of inflammatory cytokine in mediating the effect of plasma lipidome on epilepsy: a mediation Mendelian randomization study.

Background: Epilepsy is one of the most prevalent serious brain disorders globally, impacting over 70 million individuals. Observational studies have increasingly recognized the impact of plasma lipidome on epilepsy. However, establishing a direct causal link between plasma lipidome and epilepsy remains elusive due to inherent confounders and the complexities of reverse causality. This study aims to investigate the causal relationship between specific plasma lipidome and epilepsy, along with their intermediary mediators. Methods: We conducted a two-sample Mendelian randomization (MR) and mediation MR analysis to evaluate the causal effects of 179 plasma lipidomes and epilepsy, with a focus on the inflammatory cytokine as a potential mediator based on the genome-wide association study. The primary methodological approach utilized inverse variance weighting, complemented by a range of other estimators. A set of sensitivity analyses, including Cochran's Q test, I 2 statistics, MR-Egger intercept test, MR-PRESSO global test and leave-one-out sensitivity analyses was performed to assess the robustness, heterogeneity and horizontal pleiotropy of results. Results: Our findings revealed a positive correlation between Phosphatidylcholine (18:1_18:1) levels with epilepsy risk (OR = 1.105, 95% CI: 1.036-1.178, p = 0.002). Notably, our mediation MR results propose Tumor necrosis factor ligand superfamily member 12 levels (TNFSF12) as a mediator of the relationship between Phosphatidylcholine (18,1_18:1) levels and epilepsy risk, explaining a mediation proportion of 4.58% [mediation effect: (b = 0.00455, 95% CI: -0.00120-0.01030), Z = 1.552]. Conclusion: Our research confirms a genetic causal relationship between Phosphatidylcholine (18:1_18:1) levels and epilepsy, emphasizing the potential mediating role of TNFSF12 and provide valuable insights for future clinical investigations into epilepsy.

Eomesodermin expression in CD4+T-cells associated with disease progression in amyotrophic lateral sclerosis.

AIM: To clarify the role of Eomesodermin (EOMES) to serve as a disease-relevant biomarker and the intracellular molecules underlying the immunophenotype shifting of CD4+T subsets in amyotrophic lateral sclerosis (ALS). METHODS: The derivation and validation cohorts included a total of 148 ALS patients and 101 healthy controls (HCs). Clinical data and peripheral blood were collected. T-cell subsets and the EOMES expression were quantified using multicolor flow cytometry. Serum neurofilament light chain (NFL) was measured. In 1-year longitudinal follow-ups, the ALSFRS-R scores and primary endpoint events were further recorded in the ALS patients of the validation cohort. RESULTS: In the derivation cohort, the CD4+EOMES+T-cell subsets were significantly increased (p < 0.001). EOMES+ subset was positively correlated with increased serum NFL levels in patients with onset longer than 12 months. In the validation cohort, the elevated CD4+EOMES+T-cell proportions and their association with NFL levels were also identified. The longitudinal study revealed that ALS patients with higher EOMES expression were associated with higher progression rates (p = .010) and worse prognosis (p = .003). CONCLUSIONS: We demonstrated that increased CD4+EOMES+T-cell subsets in ALS were associated with disease progression and poor prognosis. Identifying these associations may contribute to a better understanding of the immunopathological mechanism of ALS.

Sex difference in the association between triglyceride and intracerebral bleeding risk after intravenous thrombolysis for acute ischemic stroke, a multi-center retrospective study.

Background: Whether the relationship of intracerebral bleeding risk with lipid profile may vary by sex remains unclear. This study aims to investigate potential sex differences in the association between lipid profile and the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) who received intravenous thrombolysis using recombinant tissue plasminogen activator (r-tPA). Methods: This multicenter retrospective observational study analyzed patients with AIS treated with intravenous r-tPA. sICH was defined as a worsening of 4 or higher points in the National Institutes of Health Stroke Scale (NIHSS) score within 36 hours after intravenous thrombolysis in any hemorrhage subtype. We assessed the odds ratio (OR) with 95% confidence interval (CI) of lipid profile for sICH for each sex using logistic regression models adjusted for potential confounding factors. Results: Of 957 participants (median age 68 (interquartile range, 59-75), men 628 (65.6%)), 56 sICH events (36 (5.7%) in men and 20 (6.1%) in women) were observed. The risk of sICH in men decreased with increasing serum levels of triglyceride after adjustment for confounding factors (vs lowest tertile, medium tertile OR 0.39, 95% CI [0.17-0.91], top tertile OR 0.33, 95% CI [0.13-0.84], overall p = 0.021; per point increase, adjusted OR 0.29, 95% CI [0.13-0.63], p = 0.002). Neither serum levels of total cholesterol nor low-density lipoprotein (LDL) was associated with sICH in men. In women, there was no association between any of the lipid levels and the risk of sICH. Conclusions: This study indicated that the association between serum levels of triglyceride and sICH may vary by sex. In men, increased triglyceride levels decrease the risk of sICH; in women, this association was lost. Further studies on the biological mechanisms for sex differences in stroke risk associated with triglyceride are needed.

Cervical and ocular vestibular evoked myogenic potentials in patients with Diabetic Peripheral Neuropathy.

BACKGROUND: Diabetes causes impaired microarterial blood flow, demyelination and neuronal damage, which may lead to cochlear damage and vestibular malfunction. Vestibular evoked myogenic potentials (VEMP) is a simple, reproducible test. Cervical and ocular vestibular evoked myogenic potentials (cVEMP and oVEMP) can be explored in the saccadic-spinal and utriculo-ocular pathways in regular clinical practice. OBJECTIVE: To evaluate possible vestibular evoked myogenic potential (VEMP) abnormalities in patients with diabetic peripheral neuropathy. MATERIALS AND METHODS: 89 patients with Type 2 Diabetes in the present study consisted of three groups: 29 patients with no peripheral neuropathy (NDPN group), 26 patients with asymptomatic neuropathy (SDPN group), 34 patients with symptomatic neuropathy (DPN group). Meanwhile, 42 healthy subjects were recruited as controls. The clinical characteristics (including gender, age, body mass index (BMI), and illness duration), as well as lipids (including triglyceride (TG), cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)), uric acid, fasting blood glucose (FBG), and glycated hemoglobin (HbA1c) were compared among the four groups. Four groups were assessed using two vestibular tests including oVEMP and cVEMP. Latency and amplitude parameters were analyzed from VEMP plots. RESULTS: The latency of n10, p15 (oVEMP), p13, n23 (cVEMP) were significantly prolonged in the SDPN and DPN groups compared with the control and NDPN groups (p < 0.01), whereas latencies were similar in NDPN and the control groups. The amplitudes were not significantly different (p > 0.05). oVEMP latency p15 and cVEMP latency (p13, n23) were positively correlated with HbA1c, FBG, and illness duration, and oVEMP latency n10 was positively correlated with HbA1c and FBG. A nomogram, including FBG, HbA1C, HDL, TG, TC, LDL and group, was constructed to predict VEMP parameters and p13 was found to be independently associated with diabetic subgroups. Receiver operating characteristic curve (ROC) analysis showed good accuracy in predicting p13 in this nomogram. A user-friendly website has been created to facilitate the application of this prediction model ( https://fyey.shinyapps.io/VEMP_Model/ ). CONCLUSION: Patients with diabetic peripheral neuropathy may have vestibular dysfunction. VEMP may be useful in assessing vestibular impairment in diabetic patients.

A nomogram to predict the treatment benefit of perampanel in drug-resistant epilepsy patients.

Objective: The objective of this study was to identify the factors that affect the efficacy of added perampanel for the treatment of drug-resistant epilepsy (DRE), and to develop a reliable nomogram to predict the benefit of this addition. Methods: A retrospective clinical analysis was conducted on DRE patients who received perampanel treatment and who were followed up for at least 6 months from January 2020 and September 2023 at the Epilepsy Center of Fujian Medical University Union Hospital. Data from January 2020 to December 2021 were used as development dataset to build model, while the data from January 2022 to September 2023 were used as validation dataset for internal validation. The predictive factors that affected the efficacy of perampanel as DRE treatment were included in the final multivariate logistic regression model, and a derived nomogram was established. Results: A total of 119 DRE patients who received perampanel treatment were included in this study (development datasets: n = 76; validation data: n = 43). Among them, 72.3% (n = 86) showed a 50% or greater reduction in seizure frequency after perampanel treatment. Of all the parameters of interest, sex, age, history of generalized tonic-clonic seizures, and the number of antiseizure medications were identified as significant predictors for estimating the benefit of adding perampanel for the treatment of DRE. A model incorporating these four variables was developed, and a nomogram was constructed to calculate the probability of benefit of adding perampanel using the model coefficients. The C-index of the predictive model was 0.838, and the validation C-index was 0.756. The goodness-of-fit test showed good calibration of the model (p = 0.920, 0.752 respectively). Conclusion: The proposed nomogram has significant clinical potential for predicting the probability of benefit of perampanel as DRE treatment. This nomogram can be used to identify DRE patients who could benefit from the early addition of perampanel to their treatment regimen.

Atrial Fibrillation and Clinical Outcomes of Endovascular Thrombectomy for Acute Ischemic Stroke: A Meta-Analysis of Adjusted Effect Estimates.

BACKGROUND: The impact of atrial fibrillation (AF) on the clinical outcomes in patients with acute ischemic stroke (AIS) who received endovascular thrombectomy remains unclear. We aimed to perform a meta-analysis of adjusted effect estimates to examine the association between the presence of AF and the clinical outcomes in patients with AIS who received endovascular thrombectomy. METHODS AND RESULTS: We searched PubMed, Embase, and the Cochrane database between January 1, 2013 and July 10, 2023. Data were meta-analyzed to compare the outcomes among patients with AIS with and without AF who received endovascular thrombectomy. Our primary outcome was 90-day functional independence defined as a modified Rankin Scale score of 0 to 2. Secondary outcomes included excellent independence (90-day modified Rankin Scale score of 0-1), 90-day mortality, symptomatic intracranial hemorrhage, and any intracranial hemorrhage. Eighteen observational studies comprising 16 096 patients with AIS (mean age, 70.1 years; women, 48.2%; 6862 with AF versus 9234 without AF) were included. There were no statistically significant differences for modified Rankin Scale score of 0 to 2 (pooled odds ratio [OR], 1.14 [95% CI, 0.95-1.37]; [95% prediction interval [PI], 0.72-1.80]), mortality (OR, 0.92 [95% CI, 0.79-1.08]; [95% PI, 0.77-1.11]), symptomatic intracranial hemorrhage (OR, 0.97 [95% CI, 0.71-1.32]; [95% PI, 0.43-2.17]), and any intracranial hemorrhage (OR, 1.08 [95% CI, 0.91-1.28]; [95% PI, 0.74-1.58]) among patients with AIS with and without AF. CONCLUSIONS: This meta-analysis detected no significant differences in 90-day functional outcomes, mortality, and intracerebral hemorrhage risk after endovascular thrombectomy in patients with AIS with and without AF. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD 42021293511.

Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels in cultured rat hippocampal neurons.

AIM: To investigate the effect of ginsenoside Rb1 on voltage-gated calcium currents in cultured rat hippocampal neurons and the modulatory mechanism. METHODS: Cultured hippocampal neurons were prepared from Sprague Dawley rat embryos. Whole-cell configuration of the patch-clamp technique was used to record the voltage-gated calcium currents (VGCCs) from the hippocampal neurons,and the effect of Rb1 was examined. RESULTS: Rb1 (2-100 µmol/L) inhibited VGCCs in a concentration-dependent manner, and the current was mostly recovered upon wash-out. The specific L-type Ca(2+) channel inhibitor nifedipine (10 µmol/L) occluded Rb1-induced inhibition on VGCCs. Neither the selective N-type Ca(2+) channel blocker ω-conotoxin-GVIA (1 µmol/L), nor the selective P/Q-type Ca(2+) channel blocker ω-agatoxin IVA (30 nmol/L) diminished Rb1-sensitive VGCCs. Rb1 induced a leftward shift of the steady-state inactivation curve of I(Ca) to a negative potential without affecting its activation kinetics or reversal potential in the I-V curve. The inhibitory effect of Rb1 was neither abolished by the adenylyl cyclase activator forskolin (10 µmol/L), nor by the PKA inhibitor H-89 (10 µmol/L). CONCLUSION: Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels, without affecting the N-type or P/Q-type Ca(2+) channels in hippocampal neurons. cAMP-PKA signaling pathway is not involved in this effect.

[Analysis of CLCN1 gene mutations in 2 patients with myotonia congenita].

OBJECTIVE: To investigate chloride channel 1 (CLCN1) gene mutation and clinical features of 2 Chinese patients with myotonia congenita. METHODS: Clinical data of a patient from a family affected with myotonia congenita in addition with a sporadic patient from Fujian province were analyzed. Exons of CLCN1 gene were amplified and sequenced. RESULTS: The proband from the affected family was found to carry a c.1024G>A heterozygous missense mutation in exon 8, whilst the sporadic patient has carried a c.1292C>T heterozygous missense mutation in exon 11. CONCLUSION: Detection of CLCN1 gene mutation is an effective method for the diagnosis of myotonia congenita. Exon 8 of CLCN1 gene may be a mutational hotspot in Chinese patients with myotonia congenita.

Diagnostic Value of Micro-Bubble Transcranial Doppler Combined with Contrast Transthoracic Echocardiography in Cryptogenic Stroke Patients with Patent Foramen Ovale.

Background: In recent years, increasing attention has been paid to cryptogenic stroke (CS) caused by the patent foramen ovale (PFO). Objective: This study aims to evaluate the value of microbubble transcranial Doppler (MB-TCD) combined with contrast transthoracic echocardiography (cTTE) in the diagnosis of cryptogenic stroke patients with PFO. Materials and Method: From January 2014 to January 2019, patients who suffered from CS were recruited and divided into the cTTE group and MB-TCD combined with cTTE group. All patients were further checked by transesophageal echocardiography (TEE). Results: A total of 130 patients accepted cTTE examination, and 109 patients accepted MB-TCD combined with cTTE. In the group, 52 of the 54 positive patients were finally confirmed by TEE with PFO, and 12 of the 76 negative patients were finally confirmed by TEE with PFO. In combined group, 50 patients were negative on both two examination (Negative group), 54 were positive on both two examination (Positive group) and finally confirmed by TEE indeed with patent foramen ovale (PFO), while remaining five (5) patients were positive only on MB-TCD (Suspected group). After checked by TEE, three (3) of five patients with MB-TCD positive were confirmed by TEE indeed with PFO. The sensitivity, specificity, positive likelihood ratio (+LR), and Youden's index of cTEE in diagnostic of cryptogenic stroke patients with PFO were 81.25%, 96.97%, 26.82 and 0.78, respectively, and these for MB-TCD combined with cTTE were 100%, 96.15%, 25.97 and 0.96, respectively. MB-TCD medium can sensitively discover PFO in cryptogenic stroke patients with 100% sensitivity and a missdiagnosis rate of 0. Conclusion: The combination of MB-TCD and cTTE can improve the sensitivity and specificity of PFO diagnosis in cryptogenic stroke patients. MB-TCD medium also had high sensitivity and specificity.

Potential Pleiotropic Genes and Shared Biological Pathways in Epilepsy and Depression Based on GWAS Summary Statistics.

Current epidemiological and experimental studies have indicated the overlapping genetic foundation of epilepsy and depression. However, the detailed pleiotropic genetic etiology and neurobiological pathways have not been well understood, and there are many variants with underestimated effect on the comorbidity of the two diseases. Utilizing genome-wide association study (GWAS) summary statistics of epilepsy (15,212 cases and 29,677 controls) and depression (170,756 cases and 329,443 controls) from large consortia, we assessed the integrated gene-based association with both diseases by Multimarker Analysis of Genomic Annotation (MAGMA) and Fisher's meta-analysis. On the one hand, shared genes with significantly altered transcripts in Gene Expression Omnibus (GEO) data sets were considered as possible pleiotropic genes. On the other hand, the pathway enrichment analysis was conducted based on the gene lists with nominal significance in the gene-based association test of each disease. We identified a total of two pleiotropic genes (CD3G and SLCO3A1) with gene expression analysis validated and interpreted twenty-five common biological process supported with literature mining. This study indicates the potentially shared genes associated with both epilepsy and depression based on gene expression, meta-data analysis, and pathway enrichment strategy along with traditional GWAS and provides insights into the possible intersecting pathways that were not previously reported.