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Introduction: Stroke, characterized by high morbidity, disability, and mortality, has become one of the major threats to human health. In recent years, many studies have begun to focus on the treatment of ischemic stroke by traditional Chinese medicine. Xuesaitong, extracted from the precious Chinese herbal medicine panax notoginseng, has shown strong neuroprotective effects in the laboratory. We conducted the present study to investigate the efficacy and safety of xuesaitong in patients with ischemic stroke. Hypothesis: For patients with ischemic stroke within 14 days of onset, the combination of xuesaitong soft capsule and aspirin can further improve the 90-day functional outcome. Methods: This multicenter, randomized, double-blind, placebo-controlled clinical trial including 3072 patients with ischemic stroke was conducted at 67 centers in China between July 30, 2018, and June 1, 2020. Eligible patients were randomly assigned to receive xuesaitong plus aspirin (xuesaitong group) or placebo plus aspirin (control group). The primary efficacy outcome was functional independence at 90 days, defined as a modified Rankin Scale score of 0 to 2. The primary safety outcome was serious adverse events at 90 days. Results: Among 3072 patients who were randomized, 2966 (96.5%) were included in the full analysis set to assess the efficacy outcome, 2970 (96.7%) were included in the safety set to assess the safety outcome. At 90 days, 1328/1487 (89.3%) patients in the xuesaitong group and 1218/1479 (82.4%) patients in the control group achieved functional independence (odds ratio, 1.79 [95% CI, 1.45-2.21]; P Conclusions: Among patients with ischemic stroke, xuesaitong plus aspirin significantly increased the likelihood of functional independence at 90 days. Trial registration: Chictr.org Identifier: ChiCTR1800016363.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and heterozygous HTRA1 mutation-related cerebral small vessel disease (CSVD) are the two types of dominant hereditary CSVD. Blood–brain barrier (BBB) failure has been hypothesized in the pathophysiology of CSVD. However, it is unclear whether there is BBB damage in the two types of hereditary CSVD, especially in heterozygous HTRA1 mutation-related CSVD. In this study, a case-control design was used with two disease groups including CADASIL (n = 24), heterozygous HTRA1 mutation-related CSVD (n = 9) and healthy controls (n = 24). All participants underwent clinical cognitive assessments and brain MRI. Diffusion-prepared pseudo-continuous arterial spin labelling was used to estimate the water exchange rate across the BBB (kw). Correlation and multiple linear regression analyses were used to examine the association between kw and disease burden and neuropsychological performance, respectively. Compared with the healthy controls, kw in the whole brain and multiple brain regions was decreased in both CADASIL and heterozygous HTRA1 mutation-related CSVD patients (Bonferroni-corrected P < 0.007). In the CADASIL group, decreased kw in the whole brain (β = −0.634, P = 0.001), normal-appearing white matter (β = −0.599, P = 0.002) and temporal lobe (β = −0.654, P = 0.001) was significantly associated with higher CSVD score after adjusting for age and sex. Reduced kw in the whole brain was significantly associated with poorer neuropsychological performance after adjusting for age, sex and education in both CADASIL and heterozygous HTRA1 mutation-related CSVD groups (β = 0.458, P = 0.001; β = 0.884, P = 0.008). This study showed that there was decreased water exchange rate across the BBB in both CADASIL and heterozygous HTRA1 mutation-related CSVD patients, suggesting a common pathophysiological mechanism underlying the two types of hereditary CSVD. These results highlight the potential use of kw for monitoring the course of CADASIL and heterozygous HTRA1 mutation-related CSVD, a possibility which should be tested in future research.

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.

ObjectiveSerum inflammatory biomarkers play crucial roles in the development of acute ischemic stroke (AIS). In this study, we explored the association between inflammatory biomarkers including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR), and clinical outcomes in AIS patients who achieved successful recanalization.MethodsPatients with AIS who underwent endovascular thrombectomy (EVT) and achieved a modified thrombolysis in the cerebral infarction scale of 2b or 3 were screened from a prospective cohort at our institution between January 2013 and June 2021. Data on blood parameters and other baseline characteristics were collected. The functional outcome was an unfavorable outcome defined by a modified Rankin Scale of 3–6 at the 3-month follow up. Other clinical outcomes included symptomatic intracranial hemorrhage (sICH) and 3-month mortality. Multivariable logistic regression analysis was performed to evaluate the effects of PLR, NLR, and MLR on clinical outcomes.ResultsA total of 796 patients were enrolled, of which 89 (11.2%) developed sICH, 465 (58.4%) had unfavorable outcomes at 3 months, and 168 (12.1%) died at the 3-month follow up. After adjusting for confounding variables, a higher NLR (OR, 1.076; 95% confidence interval [CI], 1.037–1.117; p < 0.001) and PLR (OR, 1.001; 95%CI, 1.000–1.003; p = 0.045) were significantly associated with unfavorable outcomes, the area under the receiver operating characteristic curve of NLR and PLR was 0.622 and 0.564, respectively. However, NLR, PLR, and MLR were not independently associated with sICH and 3-month mortality (all adjusted p > 0.05).ConclusionOverall, our results indicate that higher PLR and NLR were independently associated with unfavorable functional outcomes in AIS patients with successful recanalization after EVT; however, the underlying mechanisms are yet to be elucidated.

ObjectiveThis study aimed to develop and validate a nomogram to predict malignant cerebral artery infarction (MMI) after endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) in the modern thrombectomy era.MethodsWe retrospectively analyzed data from a prospective cohort of consecutive patients with AIS who underwent EVT at Xuanwu hospital between January 2013 and June 2021. A multivariable logistic regression model was employed to construct the nomogram for predicting MMI after EVT. The discrimination and calibration of the nomogram were assessed both in the derivation and validation cohorts.ResultsA total of 605 patients were enrolled in this study, with 425 in the derivation cohort and 180 in the validation cohort. The nomogram was developed based on admission systolic blood pressure (SBP), the National Institute of Health Stroke Score (NIHSS), the Alberta Stroke Program Early Computed Tomography Score (ASPECTS), vessel occlusion site, EVT time window, and recanalization status. The nomogram displayed good discrimination with the area under the receiver operating characteristics (ROCs) curve (AUC) of 0.783 [95% confidence interval (CI), 0.726–0.840] in the derivation cohort and 0.806 (95% CI, 0.738–0.874) in the validation cohort. The calibration of the nomogram was good as well, with the Hosmer–Lemeshow test of p = 0.857 in the derivation cohort and p = 0.275 in the validation cohort.ConclusionIn the modern thrombectomy era, a nomogram containing admission SBP, NIHSS, ASPECTS, vessel occlusion site, EVT time window, and recanalization status may predict the risk of MMI after EVT in patients with AIS.

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.

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.

BackgroundLipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory factor in the pathogenesis of atherosclerotic plaque and is associated with an increased risk of ischemic stroke. Whether Lp-PLA2 is associated with stenosis subtypes in acute ischemic stroke (AIS) has not been investigated.MethodsA total of 126 eligible AIS patients were divided into four groups: (1) no cerebral artery stenosis (NCS); (2) intracranial artery stenosis (ICAS); (3) extracranial artery stenosis (ECAS); and (4) combined intracranial and extracranial artery stenosis (IECS). Associations between serum Lp-PLA2 levels and the stenosis subtypes were assessed.ResultsThe ICAS group had a lower frequency of dyslipidemia as compared to the NCS group and the IECS group (35.3% vs. 70% vs. 71.8%, respectively, p = 0.001) and was more likely to be symptomatic than the ECAS group (76.5% vs. 43.8%, respectively, p = 0.014). Lp-PLA2 levels in the ICAS group were 112.2 ± 66.8 μg/L which are, higher than those in the NCS, ECAS, and IECS groups (81.7 ± 38.5, 106.1 ± 57.8, 89.3 ± 52.2 μg/L, respectively, p = 0.025). In the third and fourth quartiles of Lp-PLA2 levels, stenosis had occurred more frequently in the ICAS group than in the other three groups (third Q: 50.0% vs. 3.1% vs. 28.1% vs. 18.8%, p = 0.002; fourth Q: 48.4% vs. 16.1% vs. 25.8% vs. 9.7%, p = 0.014). Lp-PLA2 levels were higher in patients with more or severe stenosis in the ICAS group.ConclusionsElevated Lp-PLA2 levels were differentially associated with increased risk in AIS patients with ICAS compared to those with ECAS or no stenosis. Lp-PLA2 may be a promising biomarker and potential therapeutic target for ICAS.

Whether preceding transient ischemic attack (TIA) can provide neuroprotective benefits in subsequent acute ischemic stroke (AIS) caused by large vessel occlusion remains unclarified. This study aimed to investigate the association between preceding TIA and functional outcomes in AIS patients with endovascular therapy (EVT). Eligible patients were divided into TIA and non-TIA groups according to whether they experienced TIA within 96 hours prior to stroke. Two groups were balanced using propensity score matching (PSM) analysis at a 1:3 ratio. Onset stroke severity and 3-month functional independence were evaluated. A total of 887 patients were included. After PSM, 73 patients with and 217 patients without preceding TIA were well matched. Onset stroke severity was not different between the groups (p > 0.05). However, the TIA group had a lower systemic immune-inflammation index (SII) (median, 1091 versus 1358, p

We sought to explore the trends and influencing factors of the use of anticoagulants in patients with acute ischemic stroke and non-valvular atrial fibrillation (NVAF) at discharge in the era of novel oral anticoagulants (NOACs).We recruited consecutive inpatients with acute ischemic stroke and NVAF in a registered study (NCT04080830) from January 2016 to December 2021. The relevant data of patients were collected. We compared the proportions of anticoagulant treatment at discharge before and after NOACs entered China's medical insurance system. The proportion of each antithrombotic status as well as anticoagulant agents at discharge in every year were calculated, and the trends during the study period were analyzed. The relevant factors affecting anticoagulant use at discharge were further analyzed.The proportion of anticoagulation at discharge increased significantly after NOACs entered China's medical insurance system in 2018 versus before (χNOACs have indeed improved anticoagulants use in patients with acute ischemic stroke and NVAF at discharge. However, some specific factors affect anticoagulation therapy use at discharge and hinder further improvement even in the NOACs era.

Background: Secondary stroke prevention after a high-risk, non-disabling ischemic cerebrovascular event needs to be enhanced. The study was conducted to investigate whether remote ischemic conditioning (RIC) is effective in preventing recurrent ischemic events within 3 months.Methods: This was a four-center, single-arm, open-label Phase IIa futility trial (PICNIC-One Study). Adult patients (≥18 years of age) who had an acute minor ischemic stroke (AMIS) with a National Institutes of Health Stroke Scale score ≤ 3 or a transient ischemic attack (TIA) with moderate-to-high risk of stroke recurrence (ABCD score ≥ 4) within 14 days of symptom onset were recruited. Patients received RIC as adjunctive therapy to routine secondary stroke prevention regimen. RIC consisted of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs (45 min) on bilateral upper limbs twice a day for 90 days.Results: A total of 285 patients met the study criteria, of which 167 provided signed informed consent and were enrolled. Data from 162 were analyzed with five subjects excluded. Recurrent AIS/TIA occurred in 6/162 (3.7%) patients within 3 months, with no occurrence of hemorrhagic stroke. The top three adverse events were upper limb pain (44/162, 27.2%), petechia (26/162, 16.0%), and heart palpitation (5/162, 3.1%). About 68 (42.0%) subjects completed ≥ 50% of 45-min RIC sessions.Conclusions: RIC is a safe add-on procedure and it has a potential benefit in reducing recurrent cerebrovascular events in patients with high-risk, non-disabling ischemic cerebrovascular events as the risk of stroke/TIA events is lower than expected; however, its compliance needs to be improved. Our study provides critical preliminary data to plan a large sample size, randomized controlled clinical study to systematically investigate the safety and efficacy of RIC in this population.

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.

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.

Background and ObjectivesCerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a rare hereditary cerebrovascular disease caused by homozygous or compound heterozygous variations in the high-temperature requirement A serine peptidase 1 (HTRA1) gene. However, several studies in recent years have found that some heterozygousHTRA1mutations also cause cerebral small vessel disease (CSVD). The current study aims to report the novel genotypes, phenotypes, and histopathologic results of 3 pedigrees of CSVD with heterozygousHTRA1mutation.MethodsThree pedigrees of familiar CSVD, including 11 symptomatic patients and 3 asymptomatic carriers, were enrolled. Whole-exome sequencing was conducted in the probands for identifying rare variants, which were then evaluated for pathogenicity according to the American College of Medical Genetics and Genomics guidelines. Sanger sequencing was performed for validation of mutations in the probands and other family members. The protease activity was assayed for the novel mutations. All the participants received detailed clinical and imaging examinations and the corresponding results were concluded. Hematoma evacuation was performed for an intracerebral hemorrhage patient with the p.Q318H mutation, and the postoperative pathology including hematoma and cerebral small vessels were examined.ResultsThree novel heterozygousHTRA1mutations (p.Q318H, p.V279M, and p.R274W) were detected in the 3 pedigrees. The protease activity was largely lost for all the mutations, confirming that they were loss-of-function mutations. The patients in each pedigree presented with typical clinical and imaging features of CVSD, and some of them displayed several new phenotypes including color blindness, hydrocephalus, and multiple arachnoid cysts. In addition, family 1 is the largest pedigree with heterozygousHTRA1mutation so far and includes homozygous twins, displaying some variation in clinical phenotypes. More importantly, pathologic study of a patient with p.Q318H mutation showed hyalinization, luminal stenosis, loss of smooth muscle cells, splitting of the internal elastic lamina, and intramural hemorrhage/dissection-like structures.DiscussionThese findings broaden the mutational and clinical spectrum of heterozygousHTRA1-related CSVD. Pathologic features were similar with the previous heterozygous and homozygous cases. Moreover, clinical heterogeneity was revealed within the largest single family, and the mechanisms of the phenotypic heterogenetic remain unclear. Overall, heterozygous HTRA1-related CSVD should not be simply taken as a mild type of CARASIL as previously considered.

The investigation for etiology of ischemic stroke in young adults remains a diagnostic challenge. Hyoid bone–related carotid injury is a rare and under-recognized cause of ischemic stroke, without established guidelines. We describe a case of recurrent ischemic stroke in a young patient presumably attributed to an impingement of the carotid artery by an elongated hyoid bone, and present other cases reported in the literature. Based on the imaging study as well as the lack of other findings, we attributed recurrent neurovascular events to the repetitive mechanical stimulation by the elongated hyoid bone that caused a vessel wall injury with subsequent thrombus and embolus. Given repeated recurrence under antiplatelet treatment, anticoagulation was added. The following 2-year follow-up showed no new neurologic events or any other complaints. Among the young, a broad spectrum of possibilities should be considered and we call attention to this infrequent etiology of ischemic 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.

BackgroundSymptomatic intracranial hemorrhage (sICH) is a devastating complication of endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) and is associated with high risk of disability and mortality. This study intended to evaluate the predictors of sICH after EVT in patients with large vessel occlusion (LVO)-induced AIS.MethodsWe conducted a retrospective review on consecutive AIS patients who underwent EVT in our University hospital between January 2019 and August 2020. The patients were classified into two groups based upon the occurrence of sICH. The main outcomes were the occurrence of sICH using the Heidelberg Bleeding Classification and functional condition at 90 days. Multivariate logistic regression analysis and receiver operating characteristics (ROC) curves were used to identify independent predictors of sICH after EVT.ResultsThree hundred and 69 patients were enrolled in the study, of which 16.8% (n = 62) developed sICH. Favorable neurological outcome was lower in patients with sICH than in patients without sICH (6.5 vs. 43.3%; P < 0.001), with the overall mortality being 112 (30.4%) at 90 days post- EVT. Results from univariate analysis showed significant differences between the two groups in the prevalence of diabetes, initial Alberta Stroke Program Early CT Score (ASPECTS) score, National Institutes of Health Stroke Scale (NIHSS) score after operation, the levels of fasting blood glucose (FBG), neutrophil to lymphocyte ratio (NLR), platelets (PLT), and thrombin time (TT) at admission. Multivariate logistic regression analysis showed that FBG ≥ 7.54 mmol/L (OR: 2.765; 95% confidence interval [CI]: 1.513–5.054), NLR ≥ 5.48 (OR: 2.711; 95% CI: 1.433–5.128), TT at admission ≥ 16.25 s (OR: 2.022; 95% CI: 1.115–3.667), and NIHSS score within 24 h after the operation ≥ 10 (OR: 3.728; 95% CI: 1.516–9.170) were independent predictors of sICH. The combination of NLR ≥ 5.48, FBG ≥ 7.54 mmol/L, TT at admission ≥ 16.25 s, and NIHSS score within 24 h after the operation ≥ 10 generated an optimal prediction model (AUC: 0.723).ConclusionHigher levels of FDG, NLR, TT at admission, and NIHSS score after operation were associated with sICH after EVT in patients with LVO-induced AIS.

BackgroundDespite the continuing effort in investigating the preventive therapies for stroke-associated pneumonia (SAP), which is closely associated with unfavorable outcomes, conclusively effective therapy for the prevention of SAP is still lacking. Remote ischemic conditioning (RIC) has been proven to improve the survival in the sepsis model and inflammatory responses have been indicated as important mechanisms involved in the multi-organ protection effect of RIC. This study aimed to assess the safety and the preliminary efficacy of RIC in the prevention of SAP in patients with acute ischemic stroke.MethodsWe performed a proof-of-concept, pilot open-label randomized controlled trial. Eligible patients (age > 18 years) within 48 h after stroke onset between March 2019 and October 2019 with acute ischemic stroke were randomly allocated (1:1) to the RIC group and the control group. All participants received standard medical therapy. Patients in the RIC group underwent RIC twice daily for 6 consecutive days. The safety outcome included any adverse events associated with RIC procedures. The efficacy outcome included the incidence of SAP, changes of immunological profiles including mHLA-DR, TLR-2, and TLR-4 as well as other plasma parameters from routine blood tests.ResultsIn total, 46 patients aged 63.1 ± 12.5 years, were recruited (23 in each group). Overall, 19 patients in the RIC group and 22 patients in the control group completed this study. No severe adverse event was attributed to RIC procedures. The incidence of SAP was lower in the remote ischemic conditioning group (2 patients [10.5%]) than that in the control group (6 patients [27.3%]), but no significant difference was detected in both univariate and multivariate analysis (p = 0.249 and adjusted p = 0.666). No significance has been found in this pilot trial in the level of immunological profiles HLA-DR, TLR4 and TLR2 expressed on monocytes as well as blood parameters tested through routine blood tests between the two groups (p > 0.05). The IL-6 and IL-1β levels at day 5 after admission in the RIC group were lower than those in the control group (p < 0.05).InterpretationThis proof-of-concept pilot randomized controlled trial was to investigate RIC as a prevention method for SAP. Remote ischemic conditioning is safe in the prevention of SAP in patients with acute ischemic stroke. The preventive effect of RIC on SAP should be further validated in future studies.

Background: First-pass effect (FPE) is increasingly recognized as a predictor of good outcome in large vessel occlusion (LVO). This systematic review and meta-analysis aimed to elucidate the factors influencing recanalization after mechanical thrombectomy (MT) with FPE in treating acute ischemic stroke (AIS).Methods: Main databases were searched for relevant randomized controlled trials (RCTs) and observational studies reporting influencing factors of MT with FPE in AIS. Recanalization was assessed by the modified thrombolysis in cerebral ischemia (mTICI) score. Both successful (mTICI 2b-3) and complete recanalization (mTICI 2c-3) were observed. Risk of bias was assessed through different scales according to study design. The I2 statistic was used to evaluate the heterogeneity, while subgroup analysis, meta-regression, and sensitivity analysis were performed to investigate the source of heterogeneity. Visual measurement of funnel plots was used to evaluate publication bias.Results: A total of 17 studies and 6,186 patients were included. Among them, 2,068 patients achieved recanalization with FPE. The results of meta-analyses showed that age [mean deviation (MD):1.21,95% confidence interval (CI): 0.26–2.16; p = 0.012], female gender [odds ratio (OR):1.12,95% CI: 1.00–1.26; p = 0.046], diabetes mellitus (DM) (OR:1.17,95% CI: 1.01–1.35; p = 0.032), occlusion of internal carotid artery (ICA) (OR:0.71,95% CI: 0.52–0.97; p = 0.033), occlusion of M2 segment of middle cerebral artery (OR:1.36,95% CI: 1.05–1.77; p = 0.019), duration of intervention (MD: −27.85, 95% CI: −42.11–13.58; p < 0.001), time of onset to recanalization (MD: −34.63, 95% CI: −58.45–10.81; p = 0.004), general anesthesia (OR: 0.63,95% CI: 0.52–0.77; p < 0.001), and use of balloon guide catheter (BGC) (OR:1.60,95% CI: 1.17–2.18; p = 0.003) were significantly associated with successful recanalization with FPE. At the same time, age, female gender, duration of intervention, general anesthesia, use of BGC, and occlusion of ICA were associated with complete reperfusion with FPE, but M2 occlusion and DM were not.Conclusion: Age, gender, occlusion site, anesthesia type, and use of BGC were influencing factors for both successful and complete recanalization after first-pass thrombectomy. Further studies with more comprehensive observations indexes are need in the future.

Background: Rapid and effective medical care for stroke is paramount to achieve maximal functional recovery. Because of the wide spreading of the coronavirus disease in 2019 (COVID-19), acute stroke care is negatively impacted. How much acute care for stroke has been affected during the pandemic remains to be assessed.Methods: The first-level response to major public health was launched from January 24th to April 29th, 2020 in Beijing to contain the spread of COVID-19. Based on a database connecting all 77 stroke centers, the quantity and quality in emergency care for stroke during the 97 lockdown days were compared with the equivalent period in 2019. During the pandemic, 15 of the 77 stroke centers were designated to receive patients sick with COVID-19. Subgroup analyses were carried out by different types of hospitals (designated and undesignated).Results: There were 1,281 and 2,354 stroke emergency hospital admissions in the lockdown period and the parallel period in 2019, respectively. A reduction of 45.6% in admission was shown in the lockdown period, with more reductions for hemorrhagic stroke (69.0%) compared with ischemic stroke (42.9%). More reductions happened in COVID-19 designated hospitals (52.6%) compared with undesignated hospitals (41.8%). The mean NIHSS score at hospital arrival was significantly higher in the lockdown period (9.4 ± 7.7 in 2020 vs. 8.4 ± 7.8 in 2019, P < 0.001). For the metrics measuring the quality of acute stroke care, the onset to door (OTD), onset to needle (ONT), and onset to recanalization (OTR) times didn't change significantly, while significant delays are shown for the door to CT scan (DTC, 1 min delay), door to needle (DTN, 4 min delays), and door to puncture (DTP, 29 min delays) times, which mainly happened in COVID-19 undesignated hospitals.Conclusions: Profound reductions in stroke hospital admissions and significant delays in emergency care for acute ischemic stroke occurred during the pandemic of COVID-19. Engagement and effective communication with all stakeholders including patients, health care providers, governmental policymakers, and other implementation partners are required for future success in similar crises.

As severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus that causes COVID‐19, is highly infectious and variable, and given that we now understand a large proportion of asymptomatic carriers can be still infectious [1], it is expected that a normalization of epidemic prevention and control measures will be required for a long time worldwide. Our neurology department at Xuanwu Hospital in Beijing is one of the national centers for the research and treatment of neurological disorders in China.

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.

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.

ObjectivesTo investigate whether the plasma level of trimethylamine N-oxide (TMAO), a proatherosclerotic intestinal microbiota metabolite, can be a predictor of ischemic brain injury secondary to carotid artery stenting (CAS).MethodsIn 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.ResultsThe 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; p < 0.001). Increased plasma TMAO levels were associated with an increased risk of having new lesions on DWI after CAS (adjusted odds ratio for the highest vs lowest quartile, 3.85; 95% confidence interval, 1.37–7.56, p < 0.001; adjusted odds ratio for the third vs lowest quartile, 1.86; 95% confidence interval, 1.09–4.66, p = 0.02). The area under the receiver operating characteristic curve of TMAO was 0.706 for new lesions on DWI, and the optimal cutoff value was 4.29 µmol/L. The sensitivity, specificity, positive predictive value, and negative predictive value of TMAO levels ≥4.29 µmol/L for predicting new lesions on DWI were 61.5%, 74.8%, 65.5%, and 65.5%, respectively.ConclusionsIncreased TMAO levels are associated with an increased risk of new ischemic brain lesions on post-CAS MRI scans.

Introduction No licensed medications are available to treat vascular dementia (VaD). Methods Patients were randomly assigned to experimental groups (SaiLuoTong [SLT] 360 or 240 mg for groups A and B for 52 weeks, respectively) or placebo group (SLT 360 mg and 240 mg for group C only from weeks 27 to 52, respectively). Results Three hundred twenty-five patients were included in final analysis. At week 26, the difference in VaD Assessment Scale–cognitive subscale scores was 2.67 (95% confidence interval, 1.54 to 3.81) for groups A versus C, and 2.48 (1.34 to 3.62) for groups B versus C (both P

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.

Background and rationale: Although many therapies have been investigated for intracerebral hemorrhage, none have succeeded in improving the functional outcomes. Remote ischemic conditioning has been proven to promote hematoma resolution and improve neurological outcomes in an intracerebral hemorrhage model, whether it is safe and feasible in patients with intracerebral hemorrhage remains unknown. This trial aims to assess the safety, feasibility, and preliminary efficacy of remote ischemic conditioning in patients with intracerebral hemorrhage and to plan for a phase-2 study. Methods: A proof-of-concept, assessor-blinded, randomized controlled trial will be carried out with patients with intracerebral hemorrhage within 24 to 48 hours of ictus. All participants will be randomly allocated to the intervention group and the control group with a 1:1 ratio (n=20) and will be treated with standard managements according to the guidelines. Participants allocated to the intervention group will receive remote ischemic conditioning once daily for 7 consecutive days. Cranial CT examinations will be performed at baseline, and on Days 3, 7, and 14. Neurological outcomes will be assessed at baseline, and on Days 1 to 14, 30, and 90. The primary outcome to be tested is safety. Secondary tested outcomes include changes of hematoma and perihematomal edema volume, incidence of hematoma expansion, functional outcomes, and frequency of adverse events. Discussions: This study will be the first proof-of-concept randomized controlled trial to ascertain the safety, feasibility, and preliminary efficacy of remote ischemic conditioning in patients with intracerebral hemorrhage, results of which will provide parameters for future studies and provide insights into the treatment of intracerebral hemorrhage. Trial registration: Clinicaltrials.gov NCT03930940

Blood-brain barrier (BBB) damage plays an important role in overall brain injury following acute ischemic stroke (AIS). We investigated the potential utility of serum occludin, a BBB damage biomarker, in predicting the severity of AIS, hemorrhagic transformation (HT) and patient prognosis. A total of 243 patients, suspected of suffering an AIS and admitted to the emergency room at Xuanwu Hospital between November 2018 to March 2019, were enrolled in this study. Serum occludin levels were measured by enzyme linked immunosorbent assay and clinical data were collected from each patient. Receiver operating characteristic curves (ROC) were used to analyze the relationship between serum occludin and AIS. Multiple logistic regression analysis was used to analyze the relationship between serum occludin and stroke prognosis. Serum occludin levels were significantly elevated in acute stroke cases compared with those with stroke-like symptoms (P

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.

Among cerebral venous thrombosis (CVT) patients, those with venous infarction have more severe clinical presentations and worse outcomes. Identifying biomarkers associated with venous infarction in CVT may help understand the pathogenesis and provide potentially useful therapeutic markers. Fifty-two CVT patients were prospectively recruited and divided into three groups: acute/subacute CVT with venous infarction (ASVI, n=30), without venous infarction (ASOVI, n=13), and chronic CVT (n=9). Blood brain barrier (BBB) permeability-related proteins, including claudin-5, occludin, matrix metalloproteinase-9, glial fibrillary acidic protein, and S100B, and inflammation-related factor high-sensitivity C-reactive protein (hs-CRP), were tested in serum and/or cerebrospinal fluid upon admission. We compared these biomarkers between the three groups and investigated their associations with venous infarction and clinical symptom severity in acute/subacute CVT patients on admission using the NIH Stroke Scale (NIHSS). Serum hs-CRP was significantly higher in acute/subacute CVT patients than chronic CVT patients. For acute/subacute CVT patients, levels were significantly higher in the ASVI group than the ASOVI group for serum claudin-5 (medians 2.80 vs. 2.50 mg/I, respectively, P = 0.039) and hs-CRP (medians 17.25 vs. 2.27 mg/l, respectively, P = 0.003). Both these biomarkers, analyzed as categorical or continuous variables, were also significantly associated with venous infarction in acute/subacute CVT patients after logistic regression analysis. Additionally, hs-CRP was positively correlated with the NIHSS (r = 0.710, P < 0.001) on admission in acute/subacute CVT patients. In CVT patients, venous infarction was associated with BBB disruption and potentially inflammation. Hs-CRP might serve as a biomarker reflecting the clinical severity of CVT in the acute/subacute stages.

We greatly appreciate the comments made by Leslie-Mazwi et al .1 As they mentioned, the lack of a 90-day modified Rankin Scale (mRS) was a major limitation of our study. In order to share our first-hand experience as soon as possible during the pandemic, we only reported 7- day outcomes. However, the 90-day follow-up was pre-planned, as we stated in response to peer review comments. As shown in figure 1, a good clinical outcome (mRS ≤2) was seen in 52.9% (9/17) in the pandemic group compared with 39.4% (13/33) in the pre-pandemic group; this difference was not statistically significant (p=0.361). No significant difference was identified for either 90-day mortality (4/17 (23.5%) vs 5/33 (15.2%), p=0.732) or 90-day National Institutes of Health Stroke Scale score (4, IQR 1–12 vs 8, IQR 4–10; p=0.320) in the pandemic and pre-pandemic groups, respectively. However, the small sample size may partially account for this equivalence, therefore future prospective multicenter studies are warranted. Figure 1 Distribution of functional outcomes at 90 days. Modified Rankin …

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.

Objective: To investigate preliminary efficacy and safety of intravenous recombinant human pro-urokinase (rhpro-UK) in patients with acute ischemic stroke (AIS). Methods: In the 23-center phase IIa, time window stratified, randomized, open, positive controlled, clinical trial, patients within 6 hours after the onset of AIS were stratified into two therapeutic time windows. Patients within 4.5 h were randomized to receive intravenous rhpro-UK 50mg, 35mg, or recombinant tissue plasminogen activator (rt-PA; 0.9 mg/kg, maximum 90 mg). Patients within 4.5-6 h were randomized to receive rhpro-UK 50mg or 35mg. Primary outcome was a modified Rankin scale (mRS) score ≤1at 90 days. Secondary outcome was the treatment response based on ≥ 4-point reduction from the baseline National Institutes of Health stroke scale score at 24 hours after treatment. Safety outcomes included symptomatic intracerebral hemorrhage (sICH), death due to any cause, and other serious adverse events. Results: We enrolled 190 patients (Figure 1A). Within 4.5 h, the proportion of patients with a mRS score ≤1 at 90 days did not differ significantly among groups (57.9%, 55.6% and 52.6%, P=0.92). Similarly, there was no statistical significance among groups in term of treatment response at 24 hours (P=0.85). In the 4.5-6 h time window, the rates of functional independence of rhpro-UK 50mg and 35mg were 59.0% and 69.2% (P=0.34). The proportion of patients with functional response to treatment were 28.2% and 33.3% (P=0.62) (Figure1B, 1C). sICH occurred in one patient in the 50mg rphro-UK group within 4.5 h within 30 days after the intervention. There was no significant difference among the five groups in death and rate of other serious adverse events. Conclusion: As compared with rt-PA, intravenous rhpro-UK at two dose within the 4.5 hours after onset of symptoms showed similar efficacy and safety profiles in patients withAIS. Similarly, these two dose groups did not differ in efficacy and safety between 4.5-6.0 hours.

Background and Purpose: Acute/subacute cerebral venous thrombosis (CVT) with venous infarction often has poorer outcomes than CVT alone. Exploring biomarkers relevant to venous infarction and CVT severity would contribute to improved therapy and prognosis of CVT patients with venous infarction. It remains unclear whether blood-brain barrier(BBB) related proteins and hs-CRP play a crucial role in the pathogenesis of CVT with venous thrombosis. Methods: 59 Patients were divided into four groups: acute/subacute CVT patients with venous infarct(ASVI group, n=30), acute/subacute CVT patients without venous infarct(ASOVI group, n=13), chronic CVT group(n=9) and control subjects(n=7). Hs-CRP, claudin-5, occludin, MMP-9, GFAP and S100B were measured on admission in serum and/or cerebrospinal fluid(CSF). Initial CVT severity was assessed by the NIHSS. Results: In ASVI group, only serum claudin-5 and hs-CRP were significantly higher than ASOVI group (3.15±1.20 vs. 2.41±0.57, p=0.025; 19.13±15.22 vs. 5.65±6.19, P=0.001, respectively). AUCs for serum claudin-5 and Hs-CRP did not have significant difference (0.70,[95%CI:0.54-0.86]vs.0.795[95%CI:0.66-0.93], P=0.409). AUC for the combination of serum claudin-5 and hs-CRP was greater than that for claudin-5 alone (0.86 [95%CI: 0.75-0.97]vs.0.70[95%CI:0.54-0.86],P=0.0352). After adjustment, serum claudin-5 (adjusted OR, 17.85 [95% CI: 1.23-258.62], P=0.035) and hs-CRP (adjusted OR, 29.22, [95% CI:2.15-397.46], P=0.011) were significantly associated with venous infarction. When serum claudin-5 and hs-CRP were greater than or equal to their cut-off values (2.74 mg/l and 10.97mg/l), 100% of patients had venous infarcts. In ASVI group, hs-CRP was positively associated with NIHSS ( r =0.640; 95%CI, 0.340- 0.821; P&lt 0.001). Conclusions: For acute/subacute CVT patients, s erum claudin-5 and hs-CRP may be clinically valuable biomarkers associated with venous infarction. Hs-CRP was correlated with CVT severity. Anti-inflammation therapy may be useful in the management of severe CVT patients.

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.

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.

To evaluate the incidence of post-interventional contrast staining (PICS) in acute ischemic stroke (AIS) Chinese patients who were treated with endovascular thrombectomy (ET) and investigate potential association of PICS with functional outcome and intracerebral hemorrhage (ICH). This observational study was based on a single-center prospective registry study. AIS patients who underwent ET from January 2013 to February 2017 were recruited into this study. All patients had dual-energy CT (DECT) scan of the head at 12 to 24 hours post-ET. The primary outcome was the incidence of PICS. Secondary outcomes were total ICH, symptomatic ICH (sICH), 3-month functional outcome, and long-term functional outcome. One hundred and eighty patients were enrolled in this study. PICS was detected in 50 patients (28%) based on the post-interventional CT scan. We first used basic statistical analyses, showing that the incidence of both total ICH (60% vs. 25%, p

Introduction: Recently, REVASCAT and MR CLEAN studies reported favorable long-term outcome of acute ischemic stroke (AIS) patients at 1 and 2 years post endovascular thrombectomy (ET) respectively. However, no study in the real world has reported long-term outcomes of AIS after ET. Chinese patients largely experience AIS due to large artery atherosclerosis (LAA), and approximately half of them have intracranial artery stenosis. The differences of AIS patients of LAA and cardioembolism and treated with ET are unclear. In this study, we evaluate the long-term outcomes of AIS patients after ET in the real world, and investigate differences between AIS patients of different etiology. Methods: This observational study based on a prospective registry study of revascularization therapy for AIS. Favorable outcome was defined as modified Ranks scale (mRS) scores 0-2, and unfavorable outcome was defined as mRS scores 3-6. The primary outcome was mRS at the time of assessment. Results: Eighty nine subjects (aged 59.5 years old) with large artery occlusion in anterior circulation and treated with ET were recruited. Median length of follow up was 20 months (IQR 6-32), including 74% subjects longer than 12 months and 43% subjects longer than 24 months. At the time of follow up, 47 subjects (53%) achieved favorable outcome whereas 17 subjects (19%) were functional dependence and 25 subjects (28%) died. More subjects of LAA were treated with permanent intracranial stenting (22% vs. 10%) as compared with those of cardioembolism. Subjects of cardioembolism are more likely to experience sICH (19% vs. 8%) and die (32% vs. 16%) as compared with those of LAA. During the study period, 3 subjects (3.4%) had post-stroke seizures, and the incidences of recurrent stroke were 1% after 3 months, 3% after 6 months, 7% after 12 months, and 8% after 42 months Conclusions: Over half of AIS patients can achieve favorable long-term outcomes after ET. Subjects of cardioembolism are more likely to experience sICH and die.

Background and Objective: Intracranial atherosclerotic disease (ICAD) is a common etiology of stroke in China. Lipoprotein-associated phospholipaseA2 (Lp-PLA2), an inflammatory enzyme expressed in atherosclerotic plaques, has been linked to an increased risk of ischemic stroke. Relatively few studies have explored the relationship between Lp-PLA2 and various ischemic stroke subtypes. We aimed to determine the association between the serum Lp-PLA2 mass and the main types of symptomatic large vessel atherosclerosis. Methods: In this cross-sectional study, we reviewed data on 126 eligible acute ischemic stroke patients consecutively admitted to a single medical center in China from March 2014 to February 2016. Clinical symptoms, signs and traditional risk factors of cerebrovascular diseases were recorded. The level of serum lipids, homocysteine and glucose etc. were collected. Serum Lp-PLA2 and high-sensitivity C-reactive protein (hs-CRP) were measured. According to the results of CT angiography, patients were divided into four different groups: 1) no artery stenosis (N), 2) both intracranial and extracranial artery stenosis (B), 3) intracranial artery stenosis (I), 4) extracranial artery stenosis (E). The association of serum Lp-PLA2 and other inflammatory markers to ICAD were analyzed with Pearson correlation test. Results: Lp-PLA2 expression in the ICAD group was higher than other three groups (I vs. N vs. B vs. E: 112.22±66.79 ug/l vs. 81.70±38.50 ug/l vs.89.25±52.15 ug/l vs. 106.11± 57.76 ug/l, p=0.025). When Lp-PLA2 was above the median level, the presence of ICAD was higher than other three groups (Q3: 16[50.0%] vs. 1[3.1%] vs. 9[28.1%] vs. 6[18.8%], P=0.002; Q4: 15[48.4%] vs. 5[16.1%] vs. 8[25.8%] vs. 3[9.7%], P=0.014). In ICAD group, Lp-PLA2 mass was positively correlated with hs-CRP (r=0.899, P Conclusions: Lp-PLA2 is differentially associated with ICAD compared to extracranial artery stenosis or no stenosis, which suggests that inflammation may play a greater role in the pathophysiology of ICAD versus these other symptomatic stroke categories.

Introduction: Intracranial atherosclerotic disease (ICAD) is one of the most common causes of ischemic stroke worldwide. Despite aggressive medical management, the rate of recurrent stroke is 13% at 1 year. Intracranial vessel wall imaging (VWI) is a noninvasive, “looking-beyond-the-lumen” imaging method that can directly characterize the geometric and signal features of ICAD lesions. The present work sought to assess the feasibility of quantitatively monitoring regression or progression of ICAD plaques using VWI-based methods. Methods: Eight ischemic stroke patients (1F, 7M; age 27-66 ys) treated with intensive medical therapy underwent initial (4 days - 4 months of onset) and follow-up 3D VWI (6-13 months). Images were randomized and reviewed by two neuroradiologists to determine the culprit lesion in each subject. A custom-designed deep-learning-based intracranial vessel analysis method was used to segment vessel wall boundaries and quantify the following features of the culprit lesion, including peak normalized wall index (NWI), plaque volume, pre-contrast plaque-wall contrast ratio (CR), and post-contrast plaque enhancement ratio (ER). Results: No subjects except for subject #4 had a recurrent stroke during the follow-up period. The four plaque features exhibited different change patterns as shown in Figure . Subject #1 and #4 demonstrated an increase in plaque ER, volume, and peak NWI; subject #7 demonstrated an increase in plaque CR, volume and peak NWI. Other patients had a decrease or no change in these features. Conclusions: In this work, the interrogated plaque features demonstrated regression in most of patients after intensive medical therapy. Elevated values in some of these features appeared positively associated with stroke recurrence. Temporal changes in these features may have a strong indication on culprit lesions’ response to medical therapy. In conclusion, it is feasible to quantitatively monitor plaque-level treatment response.

Introduction: In real world practice, patients with minor stroke symptoms are still treated with thrombolytic therapy and majority of them recover with favorable outcomes at 90 days, but there is room to identify avenues to further enhance their outcomes. We aimed to investigate the risk factors associated with the unfavorable outcome at 90 days after thrombolysis for acute minor ischemic stroke (AMIS). Methods: 152 consecutive patients presented with AMIS (NIHSS ≤3) and received intravenous alteplase between December 2012 and February 2017. Baseline clinic-demographic, characteristics and laboratory tests were recorded. Unfavorable outcome was defined as modified Rankin Scale (mRS) of 2-6 at 90 days. Univariate analysis followed by multivariate analysis was used to identify risk factors for unfavorable outcome. A receiver operating characteristic curve was used to evaluate the predictive value. Results: 113 out of 152 patients (74%) were included in the final analysis, age 59 (53-67), 72.6% men. 32 patients (28.3%) experienced unfavorable outcomes. After adjusting for covariates, only serum glucose level on admission remained an independent factor for unfavorable outcome (OR 1.43, 95% CI: 1.10-2.72, p =0.014), with a 0.617 predictive value for the unfavorable outcome. Conclusions: About 28% of patients with AMIS in this cohort had an unfavorable outcome at 3 months after thrombolysis. Addressing higher serum glucose level on admission may be a viable therapeutic strategy to improve prognoses in these patients.

Objective: To evaluate whether claudin-5, occludin and MMP-9 proteins in serum and cerebrospinal fluid(CSF) reflect blood-brain barrier(BBB) dysfunction in cerebral venous thrombosis(CVT) with venous infarct. Methods: It is a prospective observational study. Blood and CSF samples were obtained from CVT patients in acute, subacute and chronic stages respectively. 7 healthy subjects without central nervous system disease were included as control group. Serum and CSF Claudin-5, occludin and MMP-9 were measured using ELISA kits. Values of continuous variables are presented as mean ± SD and compared with ANOVA. Results: Between Jul 2015 to Dec 2016, 52 CVT patients(age: 35.9±14.1 years; female:53.9%) were enrolled. 43 patients were at acute/ subacute stage(30 had venous infarct, while 13 did not have). 9 patients were at chronic stage. CSF occludin and MMP-9 were not detectable in most of the subjects. Serum occludin and MMP-9 were similarly expressed in all four groups. The value of CSF Claudin-5 was 257.1±44.1pg/ml for the control group, 458±223.6pg/ml for chronic CVT patients, 593.1±262.7pg/ml for acute/subacute CVT patients with venous infarct, and 529.1±334.6pg/ml for acute/subacute CVT patients without venous infarct. Compared with the control subjects, CSF Claudin-5 significantly increased in acute/subacute CVT patients with and without venous infarct(p=0.003, p=0.031, respectively). The values of CSF claudin-5 between acute/subacute CVT patients with and without venous infarct were similar (p=0.464). The value of serum Claudin-5 was 1760.6±374.2pg /ml for control subjects, 3150.7±1197.6pg/ml for acute/subacute CVT patients with venous infarct, and 2411.6±565.2pg/ml for acute/subacute CVT patients without venous infarct. Compared with control subjects, serum Claudin-5 significantly increased only in acute/subacute CVT patients with venous infarct(p=0.001), which had also significantly higher value than without venous infarct(p=0.025). Conclusions: Serum claudin-5 might reflect disruption of BBB in acute/subacute CVT patients with venous infarct. In future, larger cohorts are warranted to precisely evaluate cutoff value of serum claudin-5 in reflecting BBB dysfunction in acute/subacte CVT patients with venous infarct.