Effects of Tirofiban on Neurological Deterioration in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial.

Importance: Evidence supports using antiplatelet therapy in patients with acute ischemic stroke. However, neurological deterioration remains common under the currently recommended antiplatelet regimen, leading to poor clinical outcomes. Objective: To determine whether intravenous tirofiban administered within 24 hours of stroke onset prevents early neurological deterioration in patients with acute noncardioembolic stroke compared with oral aspirin. Design, Setting, and Participants: This investigator-initiated, multicenter, open-label, randomized clinical trial with blinded end-point assessment was conducted at 10 comprehensive stroke centers in China between September 2020 and March 2023. Eligible patients were aged 18 to 80 years with acute noncardioembolic stroke within 24 hours of onset and had a National Institutes of Health Stroke Scale (NIHSS) score of 4 to 20. Intervention: Patients were assigned randomly (1:1) to receive intravenous tirofiban or oral aspirin for 72 hours using a central, web-based, computer-generated randomization schedule; all patients then received oral aspirin. Main Outcome: The primary efficacy outcome was early neurological deterioration (increase in NIHSS score ≥4 points) within 72 hours after randomization. The primary safety outcome was symptomatic intracerebral hemorrhage within 72 hours after randomization. Results: A total of 425 patients were included in the intravenous tirofiban (n = 213) or oral aspirin (n = 212) groups. Median (IQR) age was 64.0 years (56.0-71.0); 124 patients (29.2%) were female, and 301 (70.8%) were male. Early neurological deterioration occurred in 9 patients (4.2%) in the tirofiban group and 28 patients (13.2%) in the aspirin group (adjusted relative risk, 0.32; 95% CI, 0.16-0.65; P = .002). No patients in the tirofiban group experienced intracerebral hemorrhage. At 90-day follow-up, 3 patients (1.3%) in the tirofiban group and 3 (1.5%) in the aspirin group died (adjusted RR, 1.15; 95% CI, 0.27-8.54; P = .63), and the median (IQR) modified Rankin scale scores were 1.0 (0-1.25) and 1.0 (0-2), respectively (adjusted odds ratio, 1.28; 95% CI, 0.90-1.83; P = .17). Conclusions and Relevance: In patients with noncardioembolic stroke who were seen within 24 hours of symptom onset, tirofiban decreased the risk of early neurological deterioration but did not increase the risk of symptomatic intracerebral hemorrhage or systematic bleeding. Trial Registration: ClinicalTrials.gov Identifier: NCT04491695.

Endovascular Recanalization and Standard Medical Management for Symptomatic Non-acute Intracranial Artery Occlusion: Study Protocol for a Non-randomized, 24-Month, Multicenter Study.

Background: The management of patients with symptomatic non-acute intracranial artery occlusion (sNA-ICAO), which is a special subset with high morbidity and a high probability of recurrent serious ischemic events despite standard medical therapy (SMT), has been clinically challenging. A number of small-sample clinical studies have also discussed endovascular recanalization (ER) for sNA-ICAO; however, there is currently a lack of evidence from multicenter, prospective, large-sample cohort trials. The purpose of our present study was to evaluate the technical feasibility and safety of ER for sNA-ICAO. Methods: Our group is currently undertaking a multisite, non-randomized cohort, prospective registry study enrolling consecutive patients presenting with sNA-ICAO at 15 centers in China between January 1, 2020 and December 31, 2022. A cohort of patients who received SMT and a cohort of similar patients who received ER plus SMT were constructed and followed up for 2 years. The primary outcome is any stroke from enrollment to 2 years of follow-up. The secondary outcomes are all-cause mortality, mRS score, NIHSS score and cognitive function from enrollment to 30 days, 3 months, 8 months, 12 months, 18 months, and 2 years of follow-up. Descriptive statistics and linear/logistic multiple regression models will be generated. Clinical relevance will be measured as relative risk reduction, absolute risk reduction and the number needed to treat. Discussion: The management of patients with sNA-ICAO has been clinically challenging. The current protocol aims to evaluate the technical feasibility and safety of ER for sNA-ICAO. Trial Registration Number: www.ClinicalTrials.gov, identifier: NCT04864691.

Anticoagulation delay does not affect the functional outcome of cerebral venous thrombosis.

Available knowledge about the impact of anticoagulation delay on outcomes of patients with cerebral venous thrombosis (CVT) is limited. We therefore assessed the factors influencing anticoagulation delay and investigated the effect of this delay on outcomes of CVT patients. Anticoagulation delay was defined as the time interval between symptom onset and anticoagulation initiation. The primary outcome was a modified Rankin Scale (mRS) score > 2 at the final follow-up. A total of 164 eligible patients were included. The median anticoagulation delay was 9 days. Cerebral hemorrhage on admission neuroimaging correlated with earlier anticoagulation (p = 0.040). Anticoagulation delay was not associated with poor functional outcome (mRS > 2), but it was associated with residual headache across the entire cohort (earlier anticoagulation: 15/76 [19.7%] vs. later anticoagulation: 28/79 [35.4%]; p = 0.029) and in the subgroup with isolated intracranial hypertension (earlier anticoagulation: 4/25 [16.0%] vs. later anticoagulation: 14/27 [51.9%]; p = 0.007). Anticoagulation delay was found to be common among patients with CVT. Anticoagulation delay was not associated with poor functional outcome, but may have led to an increased risk of residual headache across our entire cohort and in the subgroup with isolated intracranial hypertension.

Blood-brain Barrier Disruption May Contribute to White Matter Lesions in the Setting of Internal Jugular Venous Stenosis.

BACKGROUND AND PURPOSE: Cloudy white matter lesions are associated imaging features of internal jugular venous stenosis (IJVS). However, the mechanism of the IJVS associated cloudy white matter lesions is still unclear. This study aims to evaluate blood-brain barrier integrity of the patients with IJVS. MATERIALS AND METHODS: A total of 45 eligible patients with IJVS confirmed by computed tomography venography (CTV) and 45 healthy controls were enrolled into this study. The levels of serum MMP-9 and the markers of tight junctions, including occludin and ZO-1 obtained from IJVS patients and control group were tested by enzyme-linked immune-sorbent assay and compared. RESULTS: Both the levels of serum MMP-9 (0.2ng/ml) and occludin (0.05ng/ml) in IJVS group were higher than in the control group (0.01ng/ml vs. 0 ng/ml, all p<0.001). While, the levels of serum ZO-1 showed no statistical significance between the two groups (0.55ng/ml vs 0.735ng/ml, P=0.34). The levels of serum MMP-9 between the subset with or without white matter lesions in IJVS group showed a significant difference (0.22 [0.06, 0.43] vs. 0.01 [0.01, 0.06], P =0.019). CONCLUSION: BBB disruption may participate in the formation of IJVS-associated white matter lesions; the mechanism of BBB disruption may involve MMP-9 and occludin.

Peripheral inflammatory biomarkers in Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis.

BACKGROUND: In the past few decades, it has been demonstrated with animal models and clinical studies that a chronic inflammatory process significantly contributes to Alzheimer's disease (AD) pathogenesis. METHODS: We systematically searched on PubMed and Web of Science for studies associated with peripheral inflammatory biomarkers in AD and mild cognitive impairment (MCI) before July 2018. Meta-analysis was conducted to summarise results of studies relative to peripheral cytokines and chemokines in AD and MCI. RESULTS: Mean (± SD) concentrations of peripheral inflammatory biomarkers for AD, MCI and healthy controls were extracted from these studies. Our meta-analysis revealed consistently elevated concentrations of inflammatory biomarkers such as C-reactive protein, interleukin-1ß (IL-1ß), IL-2, IL-6, IL-12, IL-18, monocyte chemotactic protein-1 (MCP-1), MCP-3, IL-8 and interferon-γ-inducible protein 10 in AD patients, whereas no consistent results were obtained for elevated concentrations of cytokines or chemokines except MCP-1 in MCI patients. CONCLUSIONS: In conclusion, these results provided evidence to support that systematic inflammation might be a biomarker for AD diagnosis, whereas it might be a later event during AD disease progression.

Long-term Outcomes of Cerebral Venous Sinus Stenosis Corrected by Stenting.

BACKGROUND AND PURPOSE: Cerebral Venous Sinus Stenosis (CVSS) usually results in severe Intracranial Hypertension (IH), which can be corrected by stenting immediately. However, there is a lack of evidence of the long-term good outcomes in patients with CVSS who underwent stenting. METHODS: A total of 62 patients with imaging confirmed non-thrombotic and non-external compression CVSS were enrolled into this single center real-world cohort study after undergoing stenting, and were continuously followed up for more than 12 years. The symptoms and signs of IH prior to stenting and post-stenting and the incidence of restenosis after stenting were analyzed. RESULTS: The mean age of the 62 patients (range, 13 to 62) was 40 years old, and the mean body mass index was 26 (range 23 to 40). Females accounted for 67.7% (42/62). Headache was the most common symptom (79%). Transient visual obscurations occurred in 69% of the patients. 42% of the patients suffered from visual loss, 11.3% pulsatile tinnitus, and 96.8% Papilledema before stenting. The mean trans-stenotic pressure gradients were 6~43 mmHg prior to stenting and returned to 0~4 mmHg after stent placement. During the following 12~126 months (the median was 62) after stenting of the follow-up, 91.9% (57/62) of the patients obtained good outcomes. Headaches disappeared in 96% (47/49) of the patients and papilledema was attenuated in 98.3% (59/60). However, There were still 8.0 % (5/62) of the patients with poor outcomes, including optic disc atrophy in 3 patients and stent-interior thrombosis in 2 patients, which occurred 6.3 months after stenting. CONCLUSION: Our data suggest that stenting may be a promising therapy for CVSS correcting. Patients with CVSS may get long-term benefit from stenting, especially when they are accompanied with severe IH.

The comparative analysis of non-thrombotic internal jugular vein stenosis and cerebral venous sinus stenosis.

Internal jugular vein (IJV) stenosis and cerebral venous sinus (CVS) stenosis belong to cerebral venous outflow insufficiency. This study aimed to analyze the similarities and differences between IJV stenosis and CVS stenosis. Patients with either IJV stenosis or CVS stenosis confirmed by contrast-enhanced magnetic resonance venography between October 2017 and July 2018 were enrolled in this retrospective study. The similarities and differences between IJV stenosis and CVS stenosis on the aspects of clinical and imaging features were compared. A total of 82 eligible patients entered into the final analysis. The similarities of the two subsets of cerebral venous outflow insufficiency mainly included headache, head noises or tinnitus, visual disorders, and sleeping disorders, as well as cloud-like white matter hyperintensity in T2WI and FLAIR sequences of MRI. However, there were differences in between, the ratio of patients with higher intracranial pressure (ICP) was common in CVS stenosis (p < 0.001). Namely, higher ratios of papilledema (p = 0.001) and visual damage (p = 0.029), as well as poor Frisen papilledema grade scores were more commonly observed in CVS stenosis (p = 0.004), while abnormal collateral-vessels appeared more frequently in IJV stenosis (100.00%) than CVS stenosis (28.57%). Continuous head noises, tinnitus and cloud-like white matter hyperintensity in MRI are the features of both IJV stenosis and CVS stenosis. Whereas, severe headache, visual damage, papilledema, and intracranial hypertension (IH) were more common in CVS stenosis, and the appearance of collateral-vessels is a key feature of IJV stenosis.