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To evaluate pulsatility index (PI) in patients with acute ischemic stroke (AIS) who underwent endovascular thrombectomy (EVT).Patients were retrospectively recruited if their stroke were secondary to middle cerebral artery (MCA) occlusion and achieved full recanalization after EVT. Transcranial Doppler was performed within 24-hour post-EVT. The primary outcome was correlation between the MCA-PI on the affected side and 3-month functional outcome, with modified Rankin scale (mRS) ≥5 indicated extremely poor functional outcomes.Totally, 170 patients were included. High MCA-PI was positively related to the 3-month mRS score (r = 0.288, p 0.001). The highest quartile of the MCA-PI was associated with a high incidence of extremely poor functional outcomes (adjusted OR, 13.33; 95% CI, 2.65-67.17; adjusted p = 0.002) after adjusting for confounding factors. The predictive capacity of the MCA-PI for extremely poor functional outcomes was good (area under the curve, 0.755; 95% CI, 0.655-0.854; p 0.001), and its cutoff value for predicting extremely poor outcomes was 1.04, with a sensitivity of 65.6% and specificity of 78.3%.The MCA-PI on the affected side is a prognostic biomarker in patients who have undergone stroke thrombectomy. An elevated MCA-PI may be prognostically valuable for predicting extremely poor functional outcomes.

In this study, a multi-scale high-density convolutional neural network (MHCNN) classification method for spatial cognitive ability assessment was proposed, aiming at achieving the binary classification of task-state EEG signals before and after spatial cognitive training. Besides, the multi-dimensional conditional mutual information method was used to extract the frequency band features of the EEG data. And the coupling features under the combination of multi-frequency bands were transformed into multi-spectral images. At the same time, the idea of Densenet was introduced to improve the multi-scale convolutional neural network. Firstly, according to the discreteness of multispectral EEG image features, two-scale convolution kernels were used to calculate and learn useful channel and frequency band feature information in multispectral image data. Secondly, to enhance feature propagation and reduce the number of parameters, the dense network was connected after the multi-scale convolutional network, and the learning rate change function of the stochastic gradient descent algorithm was optimized to objectively evaluate the training effect. The experimental results showed that compared with the classical convolution neural network (CNN) and multi-scale convolution neural network, the proposed MHCNN had better classification performance in the six frequency band combinations with the highest accuracy of 98%: Theta-Alpha2-Gamma, Alpha2-Beta2-Gamma, Beta1-Beta2-Gamma, Theta-Beta2-Gamma, Theta- Alpha1-Gamma, and Alpha1-Alpha2-Gamma. By comparing the classification results of six frequency band combinations, it was found that the combination of the Theta-Beta2-Gamma band had the best classification effect. The MHCNN classification method proposed in this research could be used as an effective biological indicator of spatial cognitive training effect and could be extended to other brain function evaluations.

Treatment of depression with antidepressants is partly effective. Transcranial alternating current stimulation can provide a non-pharmacological alternative for adult patients with major depressive disorder. However, no study has used the stimulation to treat first-episode and drug-naïve patients with major depressive disorder. We used a randomized, double-blind, sham-controlled design to examine the clinical efficacy and safety of the stimulation in treating first-episode drug-naïve patients in a Chinese Han population. From 4 June 2018 to 30 December 2019, 100 patients were recruited and randomly assigned to receive 20 daily 40-min, 77.5 Hz, 15 mA, one forehead and two mastoid sessions of active or sham stimulation (n = 50 for each group) in four consecutive weeks (Week 4), and were followed for additional 4-week efficacy/safety assessment without stimulation (Week 8). The primary outcome was a remission rate defined as the 17-item Hamilton Depression Rating Scale (HDRS-17) score ≤ 7 at Week 8. Secondary analyses were response rates (defined as a reduction of ≥ 50% in the HDRS-17), changes in depressive symptoms and severity from baseline to Week 4 and Week 8, and rates of adverse events. Data were analysed in an intention-to-treat sample. Forty-nine in the active and 46 in the sham completed the study. Twenty-seven of 50 (54%) in the active treatment group and 9 of 50 (18%) in the sham group achieved remission at the end of Week 8. The remission rate was significantly higher in the active group compared to that in the sham group with a risk ratio of 1.78 (95% confidence interval, 1.29, 2.47). Compared with the sham, the active group had a significantly higher remission rate at Week 4, response rates at Weeks 4 and 8, and a larger reduction in depressive symptoms from baseline to Weeks 4 and 8. Adverse events were similar between the groups. In conclusion, the stimulation on the frontal cortex and two mastoids significantly improved symptoms in first-episode drug-naïve patients with major depressive disorder and may be considered as a non-pharmacological intervention for them in an outpatient setting.

Rationale There are no randomized trials examining the best treatment for acute basilar artery occlusion in the 6–24-hour time window. Aims To assess the safety and efficacy of thrombectomy for stroke due to basilar artery occlusion in patients randomized within 6–24 h from symptom onset or time last seen well. Sample size For an estimated difference of 20% in proportions of the primary outcome between the two groups, 318 patients will be included for 5% significance and 90% power with a planned interim analysis after two-thirds of the sample size (212 patients) have achieved the 90 days follow-up. Methods and design A prospective, multi-center, randomized, controlled, open-label and blinded-endpoint trial. The randomization employs a 1:1 ratio of mechanical thrombectomy with the detachable Solitaire thrombectomy device and best medical therapy (BMT) vs. BMT alone. Study outcomes The primary outcome will be the proportion of patients achieving modified Rankin Scale (mRS) 0–3 at 90 days. Key secondary outcomes are: dramatic early favorable response, dichotomized mRS score (0–2 vs. 3–6 and 0–4 vs. 5–6) at 90 days, ordinal (shift) mRS analysis at 90 days, infarct volume at 24 h, vessel recanalization at 24 h in both treatment arms, and successful recanalization in the thrombectomy arm according to the modified thrombolysis in cerebral infarction (mTICI) classification defined as mTICI 2 b or 3. Safety variables are mortality at 90 days, symptomatic intracranial hemorrhage rates at 24 h, and procedure-related complications. Discussion Results from this trial will indicate whether mechanical thrombectomy is superior to medical management alone in achieving favorable outcomes in subjects with acute stroke caused by basilar artery occlusion presenting within 6–24 h from symptom onset. Trial registration: URL: http://www.clinicaltrials.gov . ClinicalTrials.gov Identifier: NCT02737189.

This study aimed to explore the effect of different administration routes of a low dose of tirofiban on acute ischemic stroke (AIS) patients with successful recanalization after endovascular treatment (EVT).This is a cohort study that retrospectively analyzed data of patients with AIS who underwent EVT and achieved successful recanalization from a prospective registry. Eligible patients were divided into three groups according to their use of tirofiban. Propensity score matching (PSM) was used to balance baseline bias. Safety outcomes included any intracranial hemorrhage (ICH) and symptomatic ICH (sICH). Efficacy outcomes included arterial reocclusion, in-hospital mortality, 3-month mortality, and 3-month functional outcomes.We included 821 patients with 306 in the no tirofiban group, 202 in the IA + IV tirofiban group, and 313 in the IV tirofiban group. After PSM, each group included 101 patients with balanced baseline characteristics. There was no difference between the IV tirofiban group and the no tirofiban group in terms of safety and efficacy outcomes (all p 0.05). Compared with no tirofiban, IA + IV tirofiban group did not increase ICH (30.7% vs. 37.6%, p 0.05) and sICH (6.9% vs. 17.8%, p 0.05) whereas reduced 3-month mortality (14.3% vs. 28.7%, p 0.05) and improved 3-month modified Rankin Scale (median 3 vs. 4, p 0.05).A low dose of tirofiban, regardless of their administration routes, was safe for AIS patients who achieved successful recanalization with EVT, whereas only IA + IV tirofiban improved clinical outcomes.

Background Remote ischemic conditioning can promote hematoma resolution, attenuate brain edema, and improve neurological recovery in animal models of intracerebral hemorrhage. Aims This study aimed to evaluate the safety and preliminary efficacy of remote ischemic conditioning in patients with intracerebral hemorrhage. Methods In this multicenter, randomized, controlled trial, 40 subjects with supratentorial intracerebral hemorrhage presenting within 24–48 h of onset were randomly assigned to receive medical therapy plus remote ischemic conditioning for consecutive seven days or medical therapy alone. The primary safety outcome was neurological deterioration within seven days of enrollment, and the primary efficacy outcome was the changes of hematoma volume on CT images. Other outcomes included hematoma resolution rate at 7 days ([hematoma volume at 7 days − hematoma volume at baseline]/hematoma volume at baseline), perihematomal edema (PHE), and functional outcome at 90 days. Results The mean age was 59.3 ± 11.7 years and hematoma volume was 13.9 ± 4.5 mL. No subjects experienced neurological deterioration within seven days of enrollment, and no subject died or experienced remote ischemic conditioning-associated adverse events during the study period. At baseline, the hematoma volumes were 14.19 ± 5.07 mL in the control group and 13.55 ± 3.99 mL in the remote ischemic conditioning group, and they were 8.54 ± 3.99 mL and 6.95 ± 2.71 mL at seven days after enrollment, respectively, which is not a significant difference ( p > 0.05 each). The hematoma resolution rate in the remote ischemic conditioning group (49.25 ± 9.17%) was significantly higher than in the control group (41.92 ± 9.14%; MD, 7.3%; 95% CI, 1.51–13.16%; p = 0.015). The absolute PHE volume was 17.27 ± 8.34 mL in the control group and 12.92 ± 7.30 mL in the remote ischemic conditioning group at seven days after enrollment, which is not a significant between-group difference ( p = 0.087), but the relative PHE in the remote ischemic conditioning group (1.77 ± 0.39) was significantly lower than in the control group (2.02 ± 0.27; MD, 0.25; 95% CI, 0.39–0.47; p = 0.023). At 90-day follow-up, 13 subjects (65%) in the remote ischemic conditioning group and 12 subjects (60%) in the control group achieved favorable functional outcomes (modified Rankin Scale score ≤ 3), which is not a significant between-group difference ( p = 0.744). Conclusions Repeated daily remote ischemic conditioning for consecutive seven days was safe and well tolerated in patients with intracerebral hemorrhage, and it may be able to improve hematoma resolution rate and reduce relative PHE. However, the effects of remote ischemic conditioning on the absolute hematoma and PHE volume and functional outcomes in this patient population need further investigations. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT03930940.

It was reported that acupuncture could treat Alzheimer’s disease (AD) with the potential mechanisms remaining unclear. The aim of the study is to explore the effect of the combination stimulus of Hegu (LI4) and Taichong (LR3) on the resting-state brain networks in AD, beyond the default network (DMN). Twenty-eight subjects including 14 AD patients and 14 healthy controls (HCs) matched by age, gender, and educational level were recruited in this study. After the baseline resting-state MRI scans, the manual acupuncture stimulation was performed for 3 minutes, and then, another 10 minutes of resting-state fMRI scans was acquired. In addition to the DMN, five other resting-state networks were identified by independent component analysis (ICA), including left frontal parietal network (lFPN), right frontal parietal network (rFPN), visual network (VN), sensorimotor network (SMN), and auditory network (AN). And the impaired connectivity in the lFPN, rFPN, SMN, and VN was found in AD patients compared with those in HCs. After acupuncture, significantly decreased connectivity in the right middle frontal gyrus (MFG) of rFPN ( P = 0.007 ) was identified in AD patients. However, reduced connectivity in the right inferior frontal gyrus (IFG) ( P = 0.047 ) and left superior frontal gyrus (SFG) ( P = 0.041 ) of lFPN and some regions of the SMN (the left inferior parietal lobula ( P = 0.004 ), left postcentral gyrus (PoCG) ( P = 0.001 ), right PoCG ( P = 0.032 ), and right MFG ( P = 0.010 )) and the right MOG of VN ( P = 0.003 ) was indicated in HCs. In addition, after controlling for the effect of acupuncture on HCs, the functional connectivity of the right cerebellum crus I, left IFG, and left angular gyrus (AG) of lFPN showed to be decreased, while the left MFG of IFPN and the right lingual gyrus of VN increased in AD patients. These findings might have some reference values for the interpretation of the combination stimulus of Hegu (LI4) and Taichong (LR3) in AD patients, which could deepen our understanding of the potential mechanisms of acupuncture on AD.

Remote ischemic conditioning (RIC) has been demonstrated to reduce recurrent stroke in patients with intracranial artery stenosis. This study aimed to evaluate the effects of RIC in patients with the symptomatic internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion.This study is based on a high-volume single-center prospective cohort study in China, which included patients with symptomatic ICA or MCA occlusion with impaired hemodynamics and receiving chronic RIC. Clinical follow-up visits were performed regularly, and cardio-cerebrovascular events were assessed.In total, 131 patients (68 with ICA occlusion and 63 with MCA occlusion; mean age, 52.6 ± 13.7 years; stroke, 73.5%; transient ischemic attack TIA, 26.5%) qualified for the analysis; the mean follow-up period was 8.8 years (range, 3-14 years). The compliance of RIC was 95.6 ± 3.7%, and no associated severe adverse events happened. The annual risk of ischemic stroke and ischemic cerebrovascular events was 2.4% and 3.3%, respectively. The cumulative probabilities of ischemic cerebrovascular events and major adverse cardiovascular and cerebrovascular events were 32.8% and 44.8% at 14 years, respectively.In patients with symptomatic ICA or MCA occlusion with impaired hemodynamics, chronic RIC is well-tolerated, and it appears to be associated with a low annual risk of ischemic stroke and cardio-cerebrovascular events.

Previous genome-wide association studies have identified dozens of susceptibility loci for sporadic Alzheimer’s disease, but few of these loci have been validated in longitudinal cohorts. Establishing predictive models of Alzheimer’s disease based on these novel variants is clinically important for verifying whether they have pathological functions and provide a useful tool for screening of disease risk. In the current study, we performed a two-stage genome-wide association study of 3913 patients with Alzheimer’s disease and 7593 controls and identified four novel variants (rs3777215, rs6859823, rs234434, and rs2255835; Pcombined = 3.07 × 10−19, 2.49 × 10−23, 1.35 × 10−67, and 4.81 × 10−9, respectively) as well as nine variants in the apolipoprotein E region with genome-wide significance (P, Jia et al. identify novel Alzheimer’s disease-related variants in a two-stage genome-wide association study in a Chinese population, and use the variants to build 11 predictive models. Validation of the models in a separate longitudinal cohort confirms that they can predict Alzheimer's disease risk.

This systematic review and meta-analysis summarized the current literature to compare the safety and efficacy between first-pass effect (FPE) and multiple-pass effect (MPE) for thrombectomy in treatment of acute ischemic stroke (AIS). Major databases were searched for studies which reported clinical outcomes regarding successful or complete recanalization after first pass of mechanical thrombectomy in AIS. The assessment of bias was performed using different scales. I2 statistic was used to evaluate heterogeneity between reviewers. Subgroup, meta-regression, and sensitivity analyses were conducted to explore the source of heterogeneity. Visualization of funnel plots was used to evaluate publication bias. A total of 9 studies were eligible for final analysis. For successful recanalization (mTICI 2b-3), favorable outcomes were seen in 49.7% (95% confidence interval (CI): 40.5–58.9%) and 34.7% (95% CI: 26.8–42.7%) of FPE and MPE patients, respectively. Mortality at 3 months was 13.8% (95% CI: 10.8–16.9%) and 26.0% (95% CI: 17.7–34.2%), respectively. For complete recanalization (mTICI 2c-3), proportion of favorable outcomes were 62.7% (95% CI: 51.2–74.2%) and 47.7% (95% CI: 37.4–58.0%) in FPE and MPE; mortality was seen in 11.5% (95% CI: 4.9–18.2%) and 17.0% (95% CI: 5.2–28.7%), respectively. For AIS with successful recanalization, FPE had more favorable outcome (odds ratio (OR): 1.85, 95% CI: 1.48–2.30; p

BackgroundThe novel coronavirus disease 2019 (COVID-19) pandemic is still spreading across the world. Although the pandemic has an all-round impact on medical work, the degree of its impact on endovascular thrombectomy (EVT) for patients with acute ischemic stroke (AIS) is unclear.MethodsWe continuously included AIS patients with large artery occlusion who underwent EVT in a comprehensive stroke center before and during the Wuhan shutdown. The protected code stroke (PCS) for screening and treating AIS patients was established during the pandemic. The efficacy and safety outcomes including the rate of successful reperfusion (defined as modified Thrombolysis In Cerebral Infarction (mTICI) graded 2b or 3) and time intervals for reperfusion were compared between two groups: pre-pandemic and pandemic.ResultsA total of 55 AIS patients who received EVT were included. The baseline characteristics were comparable between the two groups. The time from hospital arrival to puncture (174 vs 125.5 min; p=0.002) and time from hospital arrival to reperfusion (213 vs 172 min; p=0.047) were significantly prolonged in the pandemic group compared with the pre-pandemic group. The rate of successful reperfusion was not significantly different between the two groups (85.7% (n=18) vs 88.2% (n=30); OR 0.971, 95% CI 0.785 to 1.203; p=1.000).ConclusionThe results of this study suggest a proper PCS algorithm which combines the COVID-19 screening and protection measures could decrease the impact of the disease on the clinical outcomes of EVT for AIS patients to the lowest extent possible during the pandemic.

BACKGROUND Two types of alleles exist within intron 3' and exon 8 in the presenilin 1 (PS1) gene at nucleotide 16: allele 1 (A at site 16) and allele 2 (C at site 16), and three genotypes (1/1, 1/2, and 2/2) are formed with a combination of these alleles. The present study aims to investigate the association between the intronic polymorphism of PS1 gene and the occurrence of sporadic Alzheimer's disease in a northern Chinese population. MATERIALS AND METHODS The genotype and allele frequencies of PS1 gene were compared for 90 sporadic Alzheimer's disease patients and 90 healthy controls. The intronic polymorphism of the PS1 gene was determined by the PCR-restriction fragment length polymorphism method. RESULT PS1 alleles (allele 1 [A at site 16] and allele 2 [C at site 16]) and genotypes (1/1, 1/2, and 2/2) were in Hardy-Weinberg equilibrium for both Alzheimer's disease and control subjects. The frequencies of PS1 intronic genotype 1/1 and allele 1 in the sporadic Alzheimer's disease group were significantly higher than those in the control group (P < 0.005). The genotype 2/2 was significantly lower among the patients with sporadic Alzheimer's disease compared with the controls. The onset of sporadic Alzheimer's disease was positively associated with PS1 intronic allele 1 (odds ratio = 2.14) and negatively associated with PS1 intronic allele 2 (odds ratio = 0.48). CONCLUSIONS A polymorphism of the PS1 gene is associated with sporadic Alzheimer's disease risk in a northern Chinese population. PS1 intronic allele 1 is a risk factor, and PS1 intronic allele 2 is a protective factor for sporadic Alzheimer's disease.

Background and ObjectivesTo investigate the safety and efficacy of normobaric hyperoxia (NBO) combined with endovascular treatment (EVT) in patients with acute ischemic stroke (AIS).MethodsIn this single-center, proof-of-concept, assessor-blinded, randomized, controlled pilot study, patients with AIS in the acute anterior circulation with large vessel occlusion who had an indication for EVT were randomly assigned to the EVT group or the NBO + EVT group. The NBO + EVT group was given 100% oxygen through a face mask initiated before vascular recanalization (10L/min for 4 hours), while the EVT group was given room air. The primary endpoint was infarct volume measured by MRI within 24–48 hours after randomization.ResultsA total of 231 patients were screened, and 86 patients were randomized into a ratio of 1:1 (EVT group, n = 43; NBO + EVT group, n = 43). The median infarction volume of the NBO + EVT group at 24–48 hours after randomization was significantly smaller than that of the EVT group (median 20.1 vs 37.7 mL, p < 0.01). The median mRS score at 90 days was 2 for the NBO + EVT group when compared with 3 for the EVT group (adjusted value 1.8, 95% CI 1.3–4.2; p = 0.038). Compared with the EVT group, the NBO + EVT group had a lower incidence of symptomatic intracranial hemorrhagic (7% vs 12%), mortality (9% vs 16%), and adverse events (33% vs 42%); however, such a difference was not statistically significant.DiscussionNBO in combination with EVT seems to be a safe and feasible treatment strategy that could significantly reduce infarct volume, improve short-term neurobehavioral test score, and enhance clinical outcomes at 90 days when compared with EVT alone in patients with AIS. These observations need to be further confirmed by a large, multicenter, randomized clinical trial.Clinical Trials RegistrationNCT03620370.Classification of EvidenceThis pilot study provides Class I evidence that NBO combined with standard EVT decreases infarction volume in patients with acute anterior circulation stroke.

Recombinant human prourokinase (rhPro-UK) is a novel thrombolytic that has been approved to treat patients with acute myocardial infarction. However, the safety and efficacy of intravenous rhPro-UK in patients with acute ischemic stroke (AIS) has not been well established. We aimed to investigate the safety and preliminary efficacy of rhPro-UK in patients with AIS in a multi-center phase IIa trial setting. One hundred nineteen patients within 4.5 h of AIS onset were enrolled in this randomized, open-label, 23-center phase IIa clinical trial. Patients were randomly assigned to 35 mg (n = 40) or 50 mg (n = 39) intravenous rhPro-UK or 0.9 mg/kg recombinant tissue plasminogen activator (r-tPA; n = 40). The primary endpoint was functional independence defined as a modified Rankin scale (mRS) score of 0 or 1 at 90 days. The secondary outcome was early neurological improvement defined as a reduction of ≥ 4 points on the National Institutes of Health Stroke Scale (NIHSS) score from baseline to 24 h after drug administration. Safety endpoints included death due to any cause, symptomatic intracerebral hemorrhage (sICH), and other serious adverse events (SAEs). The proportion of patients with an mRS score of ≤ 1 at 90 days did not differ significantly among three groups (35 mg rhPro-UK: 55.56% vs. 50 mg rhPro-UK: 57.89% vs. vs. r-tPA: 52.63%; P = 0.92). The rates of treatment response, referring to early neurological improvement, were similar among these three groups (36.11% vs. 31.58% vs. 28.95%, respectively; P = 0.85). There was no difference in mortality at 90 days or in the rate of other SAEs among the three groups. One patient in the 50 mg rhPro-UK group suffered sICH. While neither the primary efficacy outcomes nor safety profile differed significantly among the low, high rhPro-UK and control groups, it is a logical step to further test the low-dose rhPro-UK group versus the control group in a well-powered phase III study.Trial Registration: http://www.chictr.org.cn . Identifier: ChiCTR1800016519. Date of registration: June 6 2018.

Background: Asymptomatic intracerebral hemorrhage (AICH) is a common phenomenon in patients with acute ischemic stroke (AIS) who were treated with endovascular thrombectomy (ET). This study aimed to evaluate the clinical effects of AICH and its risk factors in this patient population. Methods: This observational study was based on a prospective registry study. AIS patients with large-vessel occlusion in the anterior circulation and treated with ET were recruited. During thrombectomy procedures, intra-arterial infusion of thrombolytics or antiplatelet and permanent stenting were used as remedial therapies. The primary outcome was the overall distribution of modified Rankin scale (mRS) 90 days after ET. Results: This study included 102 patients (61.1 ± 12.7 years old), in whom 39 patients (38.2%) experienced AICH. At 90-day follow-up, the median mRS was 2 (interquartile range [IQR] 0-3) for patients without AICH and 4 (IQR 2-6) for those with AICH (adjusted P = .005). Fourteen patients with AICH and 7 patients without AICH died, which was significantly different (35.9% versus 11.1%, adjusted P = .015). Thirty-nine patients (61.9%) without AICH and 14 patients (35.9%) with AICH achieved functional independence at 3-month follow-up (adjusted P = .117). The length of intensive care unit staying was 5 days (IQR 2-10) in patients without AICH and 8 days (IQR 3-19) in those with AICH (adjusted P = .840). In multivariate analysis, lower Alberta Stroke Program Early CT Score (ASPECTS) (adjusted P = .003) and adjunctively intra-arterial thrombolysis (adjusted P = .016) were independently associated with AICH. Conclusions: In AIS patients treated with ET AICH appears to be associated with worse functional outcomes and high mortality. Lower ASPECTS and adjectively intra-arterial thrombolysis were independent risk factors of AICH.

To estimate the impact on emergency attendance for stroke and acute myocardial infarction (AMI) during the pandemic of COVID-19 in Beijing, China. Based on 17,123 and 8693 emergency attendance for stroke and AMI, an interrupted time-series (ITS) study was conducted. Since 01/24/2020, the top two levels of regulations on major public health have been implemented in Beijing. This study covered from 03/01/2018 to 06/03/2020, including 19 weeks of lockdown period and 99 weeks before. A segmented Poisson regression model was used to estimate the immediate change and the monthly change in the secular trend of the emergency attendance rates. The emergency attendance rates of stroke and AMI cut in half at the beginning of the lockdown period, with 52.1% (95% CI 45.8% to 57.7%) and 63.1% (95% CI 56.1% to 63.1%) immediate decreases for stroke and AMI, respectively. Then during the lockdown period, 7.0% (95% CI 2.5%, 11.6%) and 16.1% (95% CI 9.5, 23.1) increases per month in the secular trends of emergency attendance rates were shown for stroke and AMI, respectively. Though the accelerated increasing rates, there were estimated 1335 and 747 patients with stroke and AMI without seeking emergency medical aid during the lockdown, respectively. The emergency attendance for stroke and AMI cut in half at the beginning of the pandemic then had gradual restoration thereafter. The results hint the need for more engagement and communications with all stakeholders to reduce the negative impact on CVD emergency medical services during the crisis. Supplementary Information The online version of this article (10.1007/s11239-021-02385-8) contains supplementary material, which is available to authorized users.

This study aims to explore an effective method to evaluate spatial cognitive ability, which can effectively extract and classify the feature of EEG signals collected from subjects participating in the virtual reality (VR) environment; and evaluate the training effect objectively and quantitatively to ensure the objectivity and accuracy of spatial cognition evaluation, according to the classification results. Therefore, a multi-dimensional conditional mutual information (MCMI) method is proposed, which could calculate the coupling strength of two channels considering the influence of other channels. The coupled characteristics of the multi-frequency combination were transformed into multi-spectral images, and the image data were classified employing the convolutional neural networks (CNN) model. The experimental results showed that the multi-spectral image transform features based on MCMI are better in classification than other methods, and among the classification results of six band combinations, the best classification accuracy of Beta1-Beta2-Gamma combination is 98.3%. The MCMI characteristics on the Beta1-Beta2-Gamma band combination can be a biological marker for the evaluation of spatial cognition. The proposed feature extraction method based on MCMI provides a new perspective for spatial cognitive ability assessment and analysis.

BackgroundNo studies have reported on how to relieve distress or relax in medical health workers while wearing medical protective equipment in coronavirus disease 2019 (COVID-19) pandemic. The study aimed to establish which relaxation technique, among six, is the most feasible in first-line medical health workers wearing medical protective equipment.MethodsThis was a two-step study collecting data with online surveys. Step 1: 15 first-line medical health workers were trained to use six different relaxation techniques and reported the two most feasible techniques while wearing medical protective equipment. Step 2: the most two feasible relaxation techniques revealed by step 1 were quantitatively tested in a sample of 65 medical health workers in terms of efficacy, no space limitation, no time limitation, no body position requirement, no environment limitation to be done, easiness to learn, simplicity, convenience, practicality, and acceptance.ResultsKegel exercise and autogenic relaxation were the most feasible techniques according to step 1. In step 2, Kegel exercise outperformed autogenic relaxation on all the 10 dimensions among the 65 participants while wearing medical protective equipment (efficacy: 24 v. 15, no space limitation: 30 v. 4, no time limitation: 31 v. 4, no body position requirement: 26 v. 4, no environment limitation: 30 v. 11, easiness to learn: 28 v. 5, simplicity: 29 v. 7, convenience: 29 v. 4, practicality: 30 v. 14, acceptance: 32 v. 6).ConclusionKegel exercise seems a promising self-relaxation technique for first-line medical health workers while wearing medical protective equipment among COVID-19 pandemic.

Background Endovascular thrombectomy (EVT) is the first-line treatment for patients with acute ischemic stroke (AIS). However, the optimal anesthetic modality during EVT is unclear. Therefore, this systematic review and meta-analysis is aimed to summarize the current literatures from RCTs to provide new clinical evidence of choosing anesthetic modality for AIS patients when receiving EVT. Methods Literature search was conducted in following databases, EMBASE, MEDLINE, Web of Science, and the Cochrane Library, for relevant randomized controlled trials (RCTs) comparing general anesthesia (GA) and conscious sedation (CS) for AIS patients during EVT. We used the Cochrane Collaboration criteria for assessment of risk bias of included studies. The heterogeneity of outcomes was assessed by I 2 statistic. Results 5 RCTs with 498 patients were included. GA was conducted in 251 patients and CS in 247 patients. EVT under GA in AIS patients had higher rates of successful recanalization (RR: 1.13, 95% CI: 1.04–1.23; P = 0.004; I2 = 40.6%) and functional independence at 3 months (RR: 1.28, 95% CI: 1.05–1.55; P = 0.013; I2 = 18.2%) than CS. However, GA was associated with higher risk of mean arterial pressure (MAP) drop (RR: 1.71, 95% CI: 1.19–2.47; P Conclusions GA was superior over CS in successful recanalization and functional independence at 3 months when performing EVT in AIS patients. However, GA was associated with higher risk of MAP drop and pneumonia. Therefore, results of ongoing RCTs will provide new clinical evidence of anesthetic modality selection during EVT in the future.

Background: The treatment of post-stroke depression (PSD) with anti-depressant drugs is partly practical. Transcranial alternating current stimulation (tACS) offers the potential for a novel treatment modality for adult patients with PSD. In this study, we will assess the efficacy and safety of tACS for treating PSD and explore its effect on gamma and beta-oscillations involving in emotional regulation. Methods: The prospective study is an 8-week, double-blind, randomized, placebo-controlled trial. Seventy eligible participants with mild to moderate PSD aged between 18 years and 70 years will be recruited and randomly assigned to either active tACS intervention group or sham group. Daily 40-minute, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4), and an additional 4-week observational period (week 8) will be followed up. The primary outcome is the proportion of participants having an improvement at week 8 according to the Hamilton Depression Rating Scale 17-Item (HAMD-17) score, including the proportion of participants having a decrease of ≥ 50% in HAMD-17 score or clinical recovery (HAMD-17 score ≤ 7). Secondary outcomes include neurological function, independence level, activities of daily living, disease severity, anxiety, and cognitive function. The exploratory outcomes are gamma and beta-oscillations assessed at baseline, week 4, and week 8. Data will be analyzed by logistical regression analyses and mixed-effects models. Discussion: The study will be the first randomized controlled trial to evaluate the efficacy and safety of tACS at a 77.5-Hz frequency and 15-mA current in reducing depressive severity in patients with PSD. The results of the study will present a base for future studies on the tACS in PSD and its possible mechanism. Trial registration number: NCT03903068, pre-results.

Objective The optimal treatment of chronic symptomatic total occlusion of the intracranial vertebral artery (ICVA) remains undefined. We report a single-center experience of endovascular recanalization for patients with chronic symptomatic ICVA occlusion who were refractory to medical therapy. Methods From Jan 2009 to Jan 2017, we retrospectively reviewed 14 consecutive patients presenting with recurrent symptoms attributed to the chronic ICVA occlusion. We searched previous literature using PubMed databases during the same period as comparison. Results Eleven patients out of 14 presented initial symptoms to intervention less than 90 days. The occlusion course was extrapolated on simultaneous two-vessel injection angiography or high-resolution MR imaging (HRMRI) in 13 cases. Nine patients had the occlusion beyond the origin of posterior inferior cerebellar artery (PICA) and 5 had the occlusion proximal to the PICA origin. The technical success rate of recanalization was 85.7% (12/14). Two patients (14.3%, 2/14) had peri-procedural complications: 1 developed TIA and 1 presented with perforator occlusion syndrome. Using the keyword-based search, we identified 6 studies at the same period. A total of 34 patients underwent recanalization with the successful recanalization rate at 94.1%, peri-procedural complication rate at 17.6% and mortality at 2.9%, respectively. Conclusion Our single-center study illustrated the feasibility and safety of ICVA recanalization. Great care should be taken as revascularization is of high risk. When patient selection, occlusion course and stage as well as neuroimaging evaluation are considered, endovascular recanalization may be a useful therapeutic modality.

Background and Purpose— The aim of the present study was to investigate atherosclerotic plaque characteristics in patients with artery-to-artery (A-to-A) embolic infarction by whole-brain high-resolution magnetic resonance imaging. Methods— Seventy-four patients (mean age, 54.7±12.1 years; 59 men) with recent stroke in the territory of middle cerebral artery because of intracranial atherosclerotic disease were prospectively enrolled. Whole-brain high-resolution magnetic resonance imaging was performed in all the patients both precontrast and postcontrast administration by using a 3-dimensional T1-weighted vessel wall magnetic resonance imaging technique known as inversion-recovery prepared sampling perfection with application-optimized contrast using different flip angle evolutions. Patients were divided into A-to-A embolic infarction and non–A-to-A embolic infarction groups based on diffusion-weighted imaging findings. The characteristics of the intracranial atherosclerotic plaques were compared between groups. Results— A total of 74 intracranial atherosclerotic plaques were analyzed (36 in A-to-A embolism group and 38 in non–A-to-A embolism group). Hyperintense plaques (HIPs) were more frequently observed in A-to-A embolism group (75.0% versus 21.1%; P P =0.029). Logistic regression analysis showed that HIP was the most powerful independent predictor of A-to-A embolic infarction ( P Conclusions— A-to-A embolic infarction has distinct vulnerable plaque characteristics compared with non–A-to-A embolic infarction. HIP and plaque surface irregularity may predict A-to-A embolic infarction.

Background: Acute minor ischemic stroke (AMIS) or transient ischemic attack (TIA) is a common cerebrovascular event with a considerable high recurrence. Prior research demonstrated the effectiveness of regular long-term remote ischemic conditioning (RIC) in secondary stroke prevention in patients with intracranial stenosis. We hypothesized that RIC can serve as an effective adjunctive therapy to pharmacotherapy in preventing ischemic events in patients with AMIS/TIA. This study aimed to investigate the feasibility, safety, and preliminary efficacy of daily RIC in inhibiting cerebrovascular/cardiovascular events after AMIS/TIA. Methods: This is a single-arm, open-label, multicenter Phase IIa futility study with a sample size of 165. Patients with AMIS/TIA receive RIC as an additional therapy to secondary stroke prevention regimen. RIC consists of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs on bilateral upper limbs twice a day for 90 days. The antiplatelet strategy is based on individual physician’s best practice: aspirin alone, clopidogrel alone, or combination of aspirin and clopidogrel. We will assess the recurrence rate of ischemic stroke/TIA within 3 months as the primary outcomes. Conclusions: The data gathered from the study will be used to determine whether a further large-scale, multicenter randomized controlled Phase II trial is warranted in patients with AMIS/TIA. Trial Registration: ClinicalTrials.gov, NCT03004820; https://www.clinicaltrials.gov/ct2/show/NCT03004820. Key words: Ischemic Preconditioning; Secondary Prevention; Stroke; Transient Ischemic Attack

Whether tirofiban is safe and effective in cardioembolic stroke patients treated with endovascular thrombectomy (EVT) remains unknown; this study evaluated the safety and efficacy of low-dose tirofiban in this patients population.This study was a prospective registry study. Patients with cardioembolic stroke undergoing EVT from January 2013 to December 2020 were treated with EVT alone or EVT plus low-dose tirofiban. The primary outcome was symptomatic intracerebral hemorrhage (sICH) prior to discharge. The secondary outcomes included reocclusion, in-hospital mortality, and 3-month functional outcomes.Overall, 288 patients were recruited and 117 received low-dose tirofiban; 137 patients (47.6%) experienced ICH, 42 patients (14.6%) were sICH, and 23 patients (8%) were fatal ICH. Thirteen patients (11.1%) receiving tirofiban and 29 patients (17.0%) not receiving tirofiban experienced sICH (p = 0.167). Reocclusion occurred in nine patients (7.7%) receiving tirofiban and 15 patients (8.8%) not receiving tirofiban (p = 0.745). The rates of hernia (6.8% versus 20.5%) and decompressive craniectomy (2.6% versus 11.7%) were significantly lower in patients receiving tirofiban (p 0.01). At 3-month follow-up, functional independence was achieved in 39 patients(33.3%) receiving tirofiban and 43 patients (25.1%) not receiving tirofiban (p = 0.131). Tirofiban was associated with lower odds of in-hospital mortality (3.4% versus 12.3%; adjusted odds ratio, 0.16; 95% confidence interval, 0.03-0.81; adjusted p = 0.027).In patients with cardioembolic stroke undergoing EVT, tirofiban is not associated with higher sICH, it seems to lead to lower odds of in-hospital death. Further investigations are needed to confirm these results and to determine the optimal treatment protocols of tirofiban.

Background and Purpose— Chinese patients largely experience acute ischemic stroke (AIS) because of large artery atherosclerosis rather than cardioembolism, and whether tirofiban is safe and effective in these patients treated with endovascular thrombectomy (ET) is unknown. This study evaluated the safety and efficacy of tirofiban in Chinese patients with AIS treated with ET. Methods— This observational study is based on a single-center prospective registry study. Patients with AIS undergoing ET with second-generation stent retrievers from January 2013 to February 2017 were treated with ET alone or ET plus low dose of tirofiban. The primary outcome was symptomatic intracerebral hemorrhage (sICH). The secondary outcomes included rate of early reocclusion, any ICH, fatal ICH, and 3-month and long-term functional outcomes. Results— One hundred eighty AIS subjects were included in the analysis, including 90 subjects treated with tirofiban and 90 subjects without tirofiban. Sixty-three subjects (35%) had any ICH, 19 of them (11%) were sICH, and 9 of them (5%) were fatal ICH. Ten subjects (11%) treated with tirofiban experienced sICH and 9 subjects (10%) not given tirofiban experienced sICH, not a significant difference ( P =0.808). Early reocclusion happened in 4 of 90 subjects (4.4%) treated with tirofiban and 8 of 90 subjects (8.9%) not treated with tirofiban ( P =0.370). One hundred sixty-one subjects (89%) completed long-term follow-up, subjects treated tirofiban were associated with lower odds of death (23% versus 44%, P =0.005) when compared with those who were not treated. Additionally, tirofiban was associated with better odds of long-term functional independence (adjusted odds ratio, 4.37; 95% confidence interval, 1.13–16.97; P =0.033). Conclusions— In patients with AIS undergoing ET, tirofiban is not associated with higher sICH, it seems to lead to lower odds of deaths and better odds of long-term functional independence. Further investigations are needed to determine the efficacy of tirofiban in preventing early reocclusion, the underlying mechanisms, and its optimal treatment protocol.

To survey the epidemiological characteristics and clinical features on epilepsy in eight ethnic groups in Yunnan province of China. Methodes The investigation was based on the WHO questionnaire and ICBERG screening questionnaire. This study was performed through random cluster sampling and door-to-door survey. Results A total of 76,302 individuals from eight ethnic groups were surveyed. The crude prevalence of epilepsy ranged from 1.2/1000 to 6.5/1000 in the eight ethnic groups, and the age-adjusted prevalence of epilepsy was from 2.1/1000 to 7.3/1000. The prevalence of active epilepsy varied from 1.0/1000 to 5.2/1000 in the eight ethnic groups, and the age-adjusted prevalence of active epilepsy was from 1.8/1000 to 6.7/1000. The age peak for seizures was below twenty, the patients of 61.1%-95.0% suffered from generalized seizures and 5%-21.2% had partial seizures. More than 60% of the cases in five ethnic groups, and the frequency of seizures were more than 10 events per year. More than 50% in other three ethnic groups, and the seizures had occurred less than 10 events per year. The treatment gap for active epilepsy ranged from 43.7% to 100.0% among the eight ethnic groups, while the natural remission rate varied from 5.6% to 21.0%. Conclusion There were both disparity and similarity in the epidemiological and clinical features of epilepsy in different ethnic group communities.

To assess whether an intensive lipid-lowering strategy is more beneficial on atherosclerotic plaque progression in the stroke survivors.We retrospectively assessed data that was prospectively collected on 106 ischemic stroke patients from one academic stroke center. Patients with various degrees of common carotid artery atherosclerosis were followed for one year. Patients were classified into intensive lipid-lowering therapy (ILLT) group if they achieve low-density lipoprotein cholesterol (LDL-c)70mg/dL (n=38) and conventional lipid-lowering therapy (CLLT) group if their LDL-c is within 70-120mg/dL (n=68) at end of one year. Carotid ultrasound was performed at baseline lipid-lowering therapy and at one year to characterize the plaques.Mean change in atherosclerotic plaque length was -1.4mm (95% CI: [-4.1, 1, 2]; P=0.27) in ILLT and 1.1mm in CLLP group (95% CI: [-0.9, 3.1]; P=0.27); no difference between groups (P=0.40). Atherosclerotic plaque thickness decreased by 0.2mm (95% CI: [-0.4, 0.03]; P=0.09) in ILLT group; while in CLLT group, thickness increased by 0.02mm after 1-year therapy (95%CI: [-0.1, 0.2]; P=0.77); no difference between groups (P=0.28).Achieving LDL-c70mg/dL in ischemic stroke patients was associated with a trend of reducing atherosclerotic plaque progression at one year. Future larger studies are warranted.

Objective Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) is considered the most effective treatment method for AIS; however, it is associated with a risk of hemorrhage. We analyzed the risk factors for digestive and urologic hemorrhage during rt-PA therapy. Methods We retrospectively analyzed patients with AIS who underwent intravenous thrombolysis with rt-PA during a 5-year period in a Chinese stroke center. Data on the demographics, medical history, laboratory test results, and clinical outcomes were collected. Results 338 patients with AIS were eligible and included. Logistic regression multivariate analysis showed that gastric catheter was significantly correlated with digestive hemorrhage, while age and urinary catheter were significantly correlated with urologic hemorrhage. Most hemorrhagic events were associated with catheterization after 1 to 24 hours of rt-PA therapy. Conclusions In summary, gastric and urinary catheters were correlated with digestive and urologic hemorrhage in patients with AIS undergoing rt-PA therapy. Well-designed controlled studies with large samples are required to confirm our findings.

ObjectiveTo investigate whether elevated plasma trimethylamine N-oxide (TMAO) levels are associated with initial stroke severity and infarct volume.MethodsThis cross-sectional study included 377 patients with acute ischemic stroke and 50 healthy controls. Plasma TMAO levels were assessed at admission. Stroke infarct size and clinical stroke severity were measured with diffusion-weighted imaging and the NIH Stroke Scale (NIHSS). Mild stroke was defined as an NIHSS score ResultsPlasma TMAO levels were higher in patients with ischemic stroke than in healthy controls (median 5.1 vs 3.0 μmol/L; p < 0.001). Every 1–µmol/L increase in TMAO was associated with a 1.13-point increase in NIHSS score (95% confidence interval [CI] 1.04–1.29; p < 0.001) and 1.69-mL increase in infarct volume (95% CI 1.41–2.03; p < 0.001) after adjustment for vascular risk factors. At admission, 159 patients (42.2%) had experienced a mild stroke, and their plasma TMAO levels were lower compared to those with moderate to severe stroke (median 3.6 vs 6.5 µmol/L; p < 0.001). The area under the receiver operating characteristics curve of plasma TMAO level in predicting moderate to severe stroke was 0.794 (95% CI 0.748–0.839; p < 0.001), and the optimal cutoff value was 4.95 μmol/L. The sensitivity and specificity of TMAO levels ≥4.95 μmol/L for moderate to severe stroke were 70.2% and 79.9%, respectively.ConclusionsPatients with ischemic stroke had higher plasma TMAO levels compared to healthy controls. Higher plasma TMAO level at admission is an independent predictor of stroke severity and infarct volume in patients with acute ischemia.

Background and Purpose. Recently, several studies indicated the c.14576G>A variant on the ring finger protein 213 (RNF213), a founder variant of moyamoya diseases (MMD), was associated with non-MMD intracranial major artery stenosis/occlusion (non-MMD ICASO). We proposed that RNF213 variant-related ICASO including MMD might be a special entity with its own characteristics based on a genetic background. The aim of the study was to learn the clinical and vascular features of RNF213 variant-related ICASO. Moreover, we tried to explore the clinical significance of a testing variant in ICASO patients in China. Methods. Clinical material and routine image data were collected in 160 Chinese patients with ICASO, including 41 verified MMD and 119 non-MMD. DNA samples were extracted, and the c.14576G>A variant on RNF213 was genotyped. Then, the clinical and vascular features were compared between the patients with and without a relevant variant. Furthermore, the patients with RNF213 mutation were performed with high resolution magnetic resonance imaging (HR-MRI) examination to conclude features of the artery wall. Results. There were 16 (10%) patients (including 9 MMD and 7 non-MMD ICASO) presenting a heterozygous c.14576G>A variant while none of homozygote was found. Compared to the patients without the c.14576G>A variant, the variant group had more female, less symptomatic patients, and more possibility of having collateral vessels in vascular imaging. In the symptomatic subgroup, there is no significant difference in clinical presentation (p>0.05) between two groups. However, RNF213 variant-related ICASO had lower scores in NIHSS (1.0±3.0 vs. 3.9±5.0, p<0.05) but not in mRS. In the symptomatic subgroup, in addition, most of the HR-MRI images of variant ICASO (77.8%, 7 of 9) were characterized by a shrunken outer diameter, concentric thickening vessel wall, and collateral vessel structures on the stenotic portion, which was prone to be diagnosed as HR-MMD (a MMD diagnosis diagnosed by HR-MRI). The rest of the two variants showed a relatively eccentric luminal narrow, normal outer diameter without collateral vessel findings, identified as HR-ICAD (intracranial atherosclerotic disease diagnosed by HR-MRI). Conclusions. Our study demonstrated that the c.14576G>A variant on RNF213 may be a biomarker to good outcome of ICASO in Chinese. The variant-related ICASO was characterized by both features of MMD and ICAD diagnosed by HR-MRI.

Background To improve the outcomes of acute ischemic stroke (AIS), timely thrombolytic therapy is crucial. Series strategies were recommended to reduce door-to-needle (DTN) time for AIS. Mobile technologies are feasible and have been used in stroke management for various purposes. However, the use of smartphone platforms that integrate series strategies through the entire first aid process to improve emergency management of AIS remains to be verified. Objective This study aims to describe the utility and application of a smartphone platform in the emergency management of AIS and report the DTN time for patients with AIS during its 2-year application period. Our results are relevant to digital health management. Methods A smartphone platform named “Green” was developed to incorporate the field assessment, hospital recommendation, prehospital notification, real-time communication, clinical records creation, key time-stamping, and quality control to streamline and standardize overall AIS emergency management processes. The emergency medical system (EMS) and all the emergency departments in Beijing have used this platform since 2018. From January 1, 2018, to December 31, 2019, 8457 patients diagnosed with AIS received intravenous tissue-type plasminogen activator therapy. The median DTN time and the proportions of patients with DTN times of ≤60 minutes and ≤45 minutes were reported. Results During the 2-year application period of this platform, the median DTN time was 45 minutes, and the proportions of patients with DTN times of ≤60 minutes and ≤45 minutes were 74.6% and 50.5%, respectively. The median DTN time was significantly reduced from 50 minutes in 2018 to 42 minutes in 2019 (P Conclusions Sustained reductions in DTN time reflected the improvement in AIS emergency management processes. The use of a smartphone platform integrating recommended strategies throughout all first aid stages is a practical way to help the emergency management of AIS.

The amygdala is an important brain area involved in cognitive procession and emotional regulation. Previous studies have typically considered the amygdala as a single structure, which likely masks contribution of individual amygdala subdivisions. Actually, the amygdala is heterogeneous and composed of structurally and functionally distinct nuclei, which may present different connectivity patterns and predict to relevant cognitive deficits in Alzheimer's disease (AD). However, little is known about functional connectivity of amygdala subregions in the resting state in AD subjects. Here, we employed resting-state functional MRI (fMRI) to examine functional connectivity changes of subregions comparing the AD patients with the age-matched control subjects. Thirty-two AD and 38 control subjects were analyzed. We defined three subregions of the amygdala according to probabilistic cytoarchitectonic atlases and mapped the whole-brain resting-state functional connectivity for each subregion: The central medial nucleus (CM) of amygdala exhibited connections with the lentiform nucleus, parahippocampus and lateral temporal gyrus; the lateral basal nucleus (LB) of amygdala functionally connected with the parahippocampus, lateral temporal gyrus, middle occipital gyrus and medial prefrontal cortex; and the superficial nucleus (SF) of amygdala had connection with the parahippocampus, lentiform nucleus, lateral temporal gyrus, insula, middle occipital gyrus, precentral and postcentral gyrus. Comparing with the controls, the AD patients presented disrupted connectivity patterns in the LB of amygdala, which predicted disconnection with the left uncus, right insula, right precentral gyrus, the left superior temporal gyrus and right claustrum. These findings in a large part supported our hypothesis and provided a new insight in understanding the pathophysiological mechanisms of AD.

Objective To investigate the feasibility and safety of remote ischemic postconditioning (RIPC) in acute ischemic stroke patients after intravenous recombinant tissue plasminogen activator (rt‐PA) thrombolysis (IVT). Methods We performed a pilot randomized trial involving acute ischemic stroke patients with IVT. The patients were randomized 1:1 to receive RIPC or standard medical therapy. In the RIPC group, the participants underwent instant RIPC within 2 h of IVT, followed by repeated RIPC therapy for 7 days. The feasibility end point was the completion of RIPC and time from the first RIPC to finishing IVT in the RIPC group. The safety end point included tissue and neurovascular injury resulting from RIPC, changes in vital signs, level of plasma myoglobin, any hemorrhagic transformation, and other adverse events. Results Thirty patients (15 RIPC and 15 Control) were recruited after IVT. The mean age was 65.7 ± 10.2 years, with a National Institutes of Health Stroke Scale (NIHSS) score of 6.5 (4.0–10.0). The completion rate for RIPC was 97.0%. The mean time from first RIPC to completing IVT was 66.0 (25.0–75.0) min in the RIPC group. One case of hemorrhagic transformation was observed in the RIPC group. No significant difference was found in the level of myoglobin between the two groups (P > 0.05). Interpretation RIPC is effective and safe for AIS patients after intravenous rt‐PA thrombolysis.

Background and Purpose: Intravenous thrombolysis is known as the only effective reperfusion therapy for acute ischemic stroke (AIS) caused by small branches occlusion. However, it is still unclear whether intra-arterial thrombolysis (IAT) is safe and effective for patients without detectable arterial occlusion. This study evaluated the safety and efficacy of IAT in these patients. Methods: Data were collected on consecutive patients from December 2012 to February 2017 at the Xuanwu Hospital, Capital Medical University. AIS patients without large artery occlusion during digital subtraction angiography (DSA) were divided into 2 groups: (1) Intra-arterial urokinase thrombolysis group (UK group): received intra-arterial urokinase thrombolysis treatment; (2) Control group: cerebral angiography examination only. The primary outcome was 3-month favorable functional outcome (modified Rankin Scale 0–2). Results: A total of 48 patients received urokinase thrombolysis, and 34 patients underwent DSA examination only. The UK group had more frequent favorable functional outcomes (70.8 vs. 50%, p = 0.032) at 3-month follow-up and higher score of National Institutes of Health Stroke Scale improvement on the second day (p = 0.007). One patient (2%) had symptomatic intracerebral hemorrhage and 3 patients (6.3%) had asymptomatic intracerebral hemorrhage (asICH) in the UK group. One patient (3.3%) had asICH in the control group. There were no significant differences about ICH. Conclusions: AIS caused by small branches occlusion could benefit from intra-arterial urokinase thrombolysis, and the risk of intracerebral hemorrhage was not significantly higher.

We report a rare case of relapsing herpes simplex encephalitis in a-37-year-old patient which was previously confirmed by positive polymerase chain reaction, herpes simplex virus (HSV) type1 IgG antibodies in cerebrospinal fluid and characterized on MRI. During the first admission, he was treated with continuous acyclovir treatment for one month with clinical improvement except for residual aphasia, for which he received a course of outpatient transcranial direct current stimulation (tDCS). A constant current of 1.2 mA was applied for 20 min twice daily. After the 4th day the patient was found to be irritable and uncooperative by staff and family members. A subsequent MRI showed significant deterioration of the lesion on comparison to the first MRI which led to discontinuation of tDCS.The relatively rapid exacerbation of HSV in only a few days is unusual. Our aim is to discuss if tDCS is related to HSV relapse and in doing so highlight possible mechanisms.

Acupuncture has been used in the therapy of Alzheimer disease (AD); however, its neural mechanisms are still unclear. The aim of this study is to examine the effect of acupuncture on the functional connectivity in AD by using resting-state functional magnetic resonance imaging (rs-fMRI). Twenty-eight subjects (14 AD and 14 normal controls) participated in this study. The rs-fMRI data were acquired before and after acupuncture stimulation at the acupoints of Tai chong (Liv3) and Hegu (LI4). During the baseline resting state, by using the amplitude of low-frequency fluctuations (ALFF), we found a significantly decreased or increased ALFF in the AD patients relative to the controls. These regions were located in the right superior frontal gyrus (SFG), left postcentral gyrus, subgenual cingulate cortex (SCC), right middle cingulate cortex (MCC), right inferior frontal gyrus (IFG), right hippocampus and the right inferior temporal gyrus (ITG). Then, we selected these brain regions as seeds to investigate whether regional activity and functional connectivity could be modulated by acupuncture in the AD patients. When compared to the pre-acupuncture stage, several of the above regions showed an increased or decreased ALFF after acupuncture in the AD patients. In addition, the functional connectivity between the hippocampus and the precentral gyrus showed enhancement after acupuncture in the AD patients. Finally, there were close correlations between the functional activity, connectivity and clinical performance in the AD patients. The current study confirmed that acupuncture at Tai chong (Liv3) and He gu (LI4) can modulate functional activity and connectivity of specific cognition-related regions in AD patients.

Neuropsychiatric disorders are increasingly conceptualized as disconnection syndromes that are associated with abnormal network integrity in the brain. However, whether different neuropsychiatric disorders show commonly dysfunctional connectivity architectures in large-scale brain networks remains largely unknown. Here, we performed a meta-connectomic study to identify disorder-related functional modules and brain regions by combining meta-analyses of 182 published resting-state functional MRI studies in 11 neuropsychiatric disorders and graph-theoretical analyses of 3 independent resting-state functional MRI datasets with healthy and diseased populations (Alzheimer's disease and major depressive disorder [MDD]). Three major functional modules, the default mode, frontoparietal, and sensorimotor networks were commonly abnormal across disorders. Moreover, most of the disorders preferred to target the network connector nodes that were primarily involved in intermodule communications and multiple cognitive components. Apart from these common dysfunctions, different brain disorders were associated with specific alterations in network modules and connector regions. Finally, these meta-connectomic findings were confirmed by two empirical example cases of Alzheimer's disease and MDD. Collectively, our findings shed light on the shared biological mechanisms of network dysfunctions of diverse disorders and have implications for clinical diagnosis and treatment from a network perspective.

Background and purpose Idiopathic intracranial hypertension (IIH) is characterized by abnormally elevated intracranial pressure (ICP) without identifiable etiology. Recently, however, a subset of patients with presumed IIH have been found with isolated internal jugular vein (IJV) stenosis in the absence of intracranial abnormalities. Methods Fifteen consecutive patients were screened from 46 patients suspected as IIH and were finally confirmed as isolated IJV stenosis. The stenotic IJV was corrected with stenting when the trans-stenotic mean pressure gradient (∆MPG) was equal to or higher than 5.44 cmH2O. Dynamic magnetic resonance venography, computed tomographic venography and digital subtraction angiography of the IJV, ∆MPG, ICP, Headache Impact Test 6 and the Frisen papilledema grade score before and after stenting were compared. Results All the stenotic IJVs were corrected by stenting. ∆MPG decreased and the abnormal collateral veins disappeared or shrank immediately. Headache, tinnitus, papilledema and ICP were significantly ameliorated at 14 ± 3 days of follow-up (all P < 0.01). At 12 ± 5.6 months of outpatient follow-up, headache disappeared in 14 out of 15 patients (93.3%), visual impairments were recovered in 10 of 12 patients (83.3%) and tinnitus resolved in 10 out of 11 patients (90.9%). In 12 out of 15 cases, the Frisen papilledema grade scores declined to 1 (0–2). The stented IJVs in all 15 patients kept to sufficient blood flows on computed tomographic venography follow-up without stenting-related adverse events. Conclusions Non-thrombotic IJV stenosis may be a potential etiology of IIH. Stenting seems to be a promising option to address the issue of intracranial hypertension from the etiological level, particularly after medical treatment failure.

To investigate whether the plasma level of trimethylamineIn this multicenter, prospective cohort study, we enrolled patients with severe carotid artery stenosis (70%) who were prepared for CAS. Plasma TMAO level was measured within 3 days before CAS, and MRI was performed 1 to 3 days after CAS.The mean age of the 268 eligible patients was 64.4 years. New lesions on diffusion-weighted imaging (DWI) were detected in 117 patients (43.7%). TMAO level was higher in patients with new (DWI) lesions than in patients without new lesions (median 5.2 vs 3.2 µmol/L;Increased TMAO levels are associated with an increased risk of new ischemic brain lesions on post-CAS MRI scans.

Serum albumin levels has been shown to predict outcome in ischemic stroke patients. We aimed to investigate the relationship between serum albumin levels and hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) in patients with acute stroke. 428 patients receiving intravenous rt-PA therapy were included from 2013 to 2016 and were categorized into two groups: low level (P > 0.05). Low level of serum albumin within 24 hours may be an independent predictor of post-thrombolytic HT.

Background and Purpose— We aimed to evaluate the efficacy of remote ischemic conditioning (RIC) in patients with cerebral small-vessel disease. Methods— Thirty patients with cerebral small-vessel disease–related mild cognitive impairment were enrolled in this prospective, randomized controlled study for 1 year. Besides routine medical treatment, participants were randomized into the experimental group (n=14) undergoing 5 cycles consisting of ischemia followed by reperfusion for 5 minutes on both upper limbs twice daily for 1 year or the control group (n=16) who were treated with sham ischemia–reperfusion cycles. The primary outcome was the change of brain lesions, and secondary outcomes were changes of cognitive function, plasma biomarkers, and cerebral hemodynamic parameters both at baseline and at the end of 1-year follow-up. Results— Compared with pretreatment, the post-treatment white matter hyperintensities volume in the RIC group was significantly reduced (9.10±7.42 versus 6.46±6.05 cm 3 ; P =0.020), whereas no significant difference was observed in the sham-RIC group (8.99±6.81 versus 8.07±6.56 cm 3 ; P =0.085). The reduction of white matter hyperintensities volume in the RIC group was more substantial than that in sham group (−2.632 versus −0.935 cm 3 ; P =0.049). No significant difference was found in the change of the number of lacunes between 2 groups (0 versus 0; P =0.694). A significant treatment difference at 1 year on visuospatial and executive ability was found between the 2 groups (0.639 versus 0.191; P =0.048). RIC showed greater effects compared with sham-RIC on plasma triglyceride (−0.433 versus 0.236 mmol/L; P =0.005), total cholesterol (−0.975 versus 0.134 mmol/L; P P =0.034), and homocysteine (−4.737 versus −1.679 µmol/L; P =0.044). Changes of the pulsation indices of middle cerebral arteries from the baseline to 1 year were different between the 2 groups (right: −0.075 versus 0.043; P =0.030; left: −0.085 versus 0.043; P =0.010). Conclusions— RIC seems to be potentially effective in patients with cerebral small-vessel disease in slowing cognition decline and reducing white matter hyperintensities. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01658306.

Background The management of blood pressure (BP) for acute ischemic stroke (AIS) patients undergoing thrombolysis is still under debate. The purpose of this study was (1) to explore the association between post-thrombolysis BP and functional outcome and (2) to examine whether post-thrombolysis BP can predict functional outcome in Chinese AIS patients undergoing thrombolysis therapy. Methods From December 2012 to November 2016, AIS patients undergoing thrombolysis were reviewed retrospectively in the Department of Neurology at Xuanwu Hospital. The BP levels were measured before and immediately after thrombolysis. Clinical outcomes, which comprised favorable outcome (modified Rankin Scale score 0-2) and unfavorable outcome (modified Rankin Scale score 3-6) at 3 months, were analyzed by logistic regression model. A receiver operating characteristic curve was used to evaluate the predictive value of post-thrombolysis BP. Results Patients with unfavorable outcome at 3 months had a higher post-thrombolysis systolic BP than those with favorable outcome (P = .015). Multivariate analysis showed that post-thrombolysis systolic BP below 159.5 mm Hg was associated with favorable outcome. According to the receiver operating characteristic curve, post-thrombolysis systolic BP was a predictor of functional outcome with an area under the curve of .573 (95% confidence interval = .504-.642). Conclusions Our study indicated that post-thrombolysis systolic BP is a predictor of functional outcome for Chinese AIS patients undergoing thrombolysis therapy. It is reasonable for AIS patients to keep post-thrombolysis systolic BP below 159.5 mm Hg to obtain a favorable outcome.

Chronic kidney disease (CKD) is gradually recognized as an independent risk factor for cardiovascular and cardio-/cerebrovascular disease. This study aimed to examine the association of the estimated glomerular filtration rate (eGFR) and clinical outcomes at 3 months after the onset of ischemic stroke in a hospitalized Chinese population. Totally, 972 patients with acute ischemic stroke were enrolled into this study. Modified of Diet in Renal Disease (MDRD) equations were used to calculate eGFR and define CKD. The site and degree of the stenosis were examined. Patients were followed-up for 3 months. Endpoint events included all-cause death and newly ischemic events. The multivariate logistic model was used to determine the association between renal dysfunction and patients’ outcomes. Of all patients, 130 patients (13.4%) had reduced eGFR (

Background Epidemiologic studies on mild cognitive impairment (MCI) are limited in China. Methods Using a multistage cluster sampling design, a total of 10,276 community residents (6096 urban, 4180 rural) aged 65 years or older were evaluated and diagnosed with normal cognition, MCI, or dementia. MCI was further categorized by imaging into MCI caused by prodromal Alzheimer's disease (MCI-A), MCI resulting from cerebrovascular disease (MCI-CVD), MCI with vascular risk factors (MCI-VRF), and MCI caused by other diseases (MCI-O). Results The prevalences of overall MCI, MCI-A, MCI-CVD, MCI-VRF, and MCI-O were 20.8% (95% confidence interval [CI] = 20.0–21.6%), 6.1% (95% CI = 5.7–6.6%), 3.8% (95% CI = 3.4–4.2%), 4.9% (95% CI = 4.5–5.4%), and 5.9% (95% CI = 5.5–6.4%) respectively. The rural population had a higher prevalence of overall MCI (23.4% vs 16.8%, P Conclusions The prevalence of MCI in elderly Chinese is higher in rural than in urban areas. Vascular-related MCI (MCI-CVD and MCI-VRF) was most common.

Acute and subacute cognitive decline, defined collectively as rapid cognitive impairment (RCI), is attributed to diverse disorders and brings great challenges for differential diagnosis. In this study we investigated the RCI patients to determine the underlying causes and the cognitive outcome of the treatable RCI.We reviewed medical records of consecutively hospitalized patients (n = 346) with significant and new cognitive dysfunction between January 2014 and December 2015. Based on the duration of their cognitive dysfunction, patients were divided into two groups with the RCI (12 months) and the chronic cognitive impairment (CCI, ≥ 12 months), respectively. Etiologies of the RCI and the CCI were analyzed; the cognitive outcomes of the RCI patients with the treatable disorders were assessed in the follow-up visits.Potentially treatable or reversible causes were identified in 134 (72%) of 187 RCI patients and in 34 (21%) of 159 CCI patients. The causes in the 134 (72%) RCI patients were immune/inflammation (50, 37%), infection (30, 22%), vascular diseases (29, 22%), neoplasm (16, 12%), metabolic/toxic disorders (7, 5%), and others (2, 1%). The treatable disorders found in both the RCI and the CCI patients were vascular diseases, autoimmune encephalitis, viral encephalitis, inflammatory demyelinating diseases, Hashimoto encephalopathy, neurosyphilis, hydrocephalus, and Vitamin B12 deficiency. Total 114 RCI patients with the treatable disorders were followed up for 6∼39 (median 21) months. Poor cognitive outcomes were found in 24 (21%) of the 114 followed-up patients, comprising patients with infection (1, 3%), immune/inflammation (12, 25%), vascular diseases (8, 28%), and metabolic/toxic disorders (3, 43%).Treatable or reversible causes are common underlying RCI. Poor outcomes with severe cognitive deficits are considerably present in the treatable RCI patients and result in permanent dementia.

Objectives We aim to demonstrate the effects of time delays on the therapeutic outcomes of intravenous thrombolysis (IVT) in acute posterior circulation stroke (PCS) patients. Methods Consecutive PCS cases treated with IVT alone were retrospectively examined. The primary end point was set to be a favorable outcome (modified Rankin Scale [mRS] ≤2) at 3 months, and angiographic recanalization was set to be the secondary outcome. Results A total of 95 PCS cases with IVT were recruited. The patients with favorable outcomes and those without favorable outcomes had similar baseline characteristics, except for significantly lower National Institute of Health Stroke Scale (NIHSS) scores (5 vs. 12, respectively; p

The Chinese population has been aging rapidly and the country's economy has experienced exponential growth during the past three decades. The goal of this study was to estimate the changes in the prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) among elderly Chinese individuals and to analyze differences between urban and rural areas.For the years 2008 to 2009, we performed a population-based cross-sectional survey with a multistage cluster sampling design. Residents aged 65 years and older were drawn from 30 urban (n = 6096) and 45 rural (n = 4180) communities across China. Participants were assessed with a series of clinical examinations and neuropsychological measures. Dementia, AD, and VaD were diagnosed according to established criteria via standard diagnostic procedures.The prevalence of dementia, AD, and VaD among individuals aged 65 years and older were 5.14% (95% CI, 4.71-5.57), 3.21% (95% CI, 2.87-3.55), and 1.50% (95% CI, 1.26-1.74), respectively. The prevalence of dementia was significantly higher in rural areas than in urban ones (6.05% vs. 4.40%, P.001). The same regional difference was also seen for AD (4.25% vs. 2.44%, P.001) but not for VaD (1.28% vs. 1.61%, P = .166). The difference in AD was not evident when the sample was stratified by educational level. Moreover, the risk factors for AD and VaD differed for urban and rural populations.A notably higher prevalence of dementia and AD was found in rural areas than in urban ones, and education might be an important reason for the urban-rural differences.

Active smokers with myocardial infarction were shown to have enhanced benefit with clopidogrel compared with aspirin. Whether this "paradox" exists in ischemic stroke patients is unknown. We aimed to investigate whether smoking status has a differential impact on the efficacy of clopidogrel vs. aspirin in patients with non-cardioembolic strokes.This single-center study retrospectively assessed 1792 non-cardioembolic ischemic stroke patients discharged from January 2013 to October 2014, and followed for 12months. Patients were categorized as current-smokers and never-smokers. Primary outcome was a composite of secondary ischemic stroke, myocardial infarction and all-cause death. Secondary outcome was secondary ischemic stroke.1066 patients were current-smokers and 726 were never-smokers. Compared with never-smokers, current-smokers had significantly higher rates of ischemic stroke (4.3% vs. 1.2%; adjusted OR: 3.60, 95%CI: 1.50-8.64, p=0.004). Regarding the primary outcome, among smokers, rates showed a lower trend in clopidogrel vs. aspirin groups (3.7% vs. 6.4%; adjusted OR 0.57, 95%CI: 0.31-1.07, p=0.08), but no difference among never-smokers (2.1% vs. 1.0%; adjusted OR: 1.67, 95%CI: 0.47-5.89, p=0.42). Similarly, among smokers, trending lower rates for recurrent ischemic stroke were observed in clopidogrel vs. aspirin group (3.1% vs. 5.0%; adjusted OR: 0.60, 95%CI: 0.31-1.18, p=0.14); but no difference between the two groups among never-smokers (1.7% vs. 1.0%; adjusted OR 1.36, 95%CI: 0.36-5.52, p=0.65).Smoking is a major risk factor for recurrent stroke in our retrospective non-cardioembolic ischemic stroke cohort. Active-smokers trend toward better cardiovascular outcomes when on clopidogrel. This finding needs to be confirmed in a prospective cohort.

To compare the outcomes of intracranial stent implantation and medical therapy for treatment of severe intracranial stenosis.Articles were identified from Medline, Cochrane, EMBASE, and Google Scholar published up to August 25, 2016. Eligible studies reported stroke occurrence, transient ischemic attack (TIA), and event-free survival rates in patients who suffered recent TIA or stroke caused by stenosis of a major intracranial artery and treated with either medical therapy or stenting. 4 studies enrolled a total 739 patients.While no association between intracranial endovascular therapy and short-term stroke risk was found (pooled OR=1.349, 95% CI=0.541 to 3.367, P=0.521), significantly higher rate of stroke occurrence was observed in patients treated with stent therapy within 30days of treatment (pooled OR=3.143, 95% CI=1.755 to 5.628, P0.001). No association was found between the type of treatment and TIA occurrence (pooled OR=0.702, 95% CI=0.277 to 1.781, P=0.457) and event-free survival rate (pooled HR=1.170, 95% CI=0.947 to 1.447, P=0.145).Patients with symptomatic intracranial atherosclerotic stenosis undergoing stent therapy may have higher risk of short-term stroke.