Stroke and Vascular Neurology最新文献

Background: Perforating artery territorial infarction (PAI) caused by branch atheromatous disease (BAD) is prone to recurrence and early progression without an effective and well-documented antiplatelet treatment regimen. Tirofiban, an adjunctive antiplatelet agent, has shown great potential to treat acute ischaemic stroke. However, whether the combination of tirofiban and aspirin can improve the prognosis of PAI remains unclear.

Aim: To explore an effective and safe antiplatelet regimen for reducing the risk of recurrence and early neurological deterioration (END) in PAI caused by BAD by comparing the tirofiban and aspirin combination with placebo and aspirin combination.

Methods: Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction (STRATEGY) trial is an ongoing multicentre, randomised, placebo-controlled trial in China. Eligible patients shall be randomly assigned to receive standard aspirin with tirofiban or placebo on the first day and standard aspirin from days 2 to 90. The primary endpoint is a new stroke or END within 90 days. The primary safety endpoint is severe or moderate bleeding within 90 days.

Discussion: The STRATEGY trial will assess whether tirofiban combined with aspirin is effective and safe in preventing recurrence and END in patients with PAI.

Trial registration number: NCT05310968.

Background and purpose: Clinical studies have demonstrated that edaravone dexborneol can improve the functional outcomes in patients with acute ischaemic stroke (AIS). The present clinical trial aimed at testing the efficacy and safety of Y-2 sublingual tablet on 90-day functional outcome in patients with AIS.

Methods and design: This is a randomised, double-blind, placebo-controlled, multicentre, parallel-group trial of Y-2 sublingual tablet on patients with AIS.An estimated 914 patients at age of 18-80 years with AIS within 48 hours after symptom onset from 40 hospitals will be randomly assigned to receive Y-2 sublingual tablet or placebo for 14 days. Patients are at score 6-20 points on National Institutes of Health Stroke Scale (NIHSS) and had a modified Rankin Scale (mRS) ≤1 before this stroke, except mechanical thrombectomy and neuroprotective agents treatment.

Study outcomes: The primary outcome is the proportion of patients with mRS ≤1 on day 90 after randomisation. Secondary efficacy outcomes include mRS score on day 90, the proportion of patients with mRS ≤2 on day 90; the change of NIHSS score from baseline to day 14 and the proportion of patients with NIHSS score ≤1 at the days 14, 30 and 90.

Discussion: This trial will provide valuable evidence for the efficacy and safety of Y-2 sublingual table for improving 90 days the functional outcomes in patients with AIS.

Trial registration number: NCT04950920.

Background and purpose: Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) was not inferior to alteplase for ischaemic stroke within 4.5 hours. Our study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion (LVO) of anterior circulation beyond 4.5 hours.

Methods and design: Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-III (TRACE III) is a multicentre, prospective, randomised, open-label, blind endpoint, controlled clinical trial. Patients who had an ischaemic stroke due to anterior circulation LVO (internal carotid artery, middle cerebral artery M1 and M2 segments) within 4.5-24 hours from last known well (including wake-up stroke and no witness stroke) and with salvageable tissue (ischaemic core volume <70 mL, mismatch ratio ≥1.8 and mismatch volume ≥15 mL) based on CT perfusion or MRI perfusion-weighted imaging (PWI) were included and randomised to rhTNK-tPA 0.25 mg/kg (single bolus) to a maximum of 25 mg or standard medical therapy. Specially, we will exclude patients who are intended for direct thrombectomy. All will be followed up for 90 days.

Study outcomes: Primary efficacy outcome is modified Rankin Scale (mRS) score ≤1 at 90 days. Secondary efficacy outcomes include ordinal distribution of mRS at 90 days, major neurological improvement defined by a decrease ≥8 points compared with the initial deficit or a score ≤1 on the National Institutes of Health Stroke Scale (NIHSS) at 72 hours, mRS score ≤2 at 90 days, the rate of improvement on Tmax >6 s at 24 hours and NIHSS score change from baseline at 7 days. Safety outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 days.

Discussion: TRACE III will provide evidence for the efficacy and safety of rhTNK-tPA in patients who had an ischaemic strokes due to anterior circulation LVO beyond 4.5 hours.

Trial registration number: NCT05141305.

Introduction: It remains unclear whether enlarged perivascular spaces (EPVS) predict poor clinical outcomes in patients with acute ischaemic stroke (AIS) or transient ischaemic attack (TIA).

Method: Data were obtained from the Third China National Stroke Registry study. We estimated EPVS in basal ganglia (BG) and centrum semiovale (CSO) using a semiquantified scale (Grade from 0 to 4). Using Cox and logistic regression analyses, the associations of EPVS with 3-month and 1-year adverse outcomes (including recurrent stroke, ischaemic stroke, haemorrhagic stroke, combined vascular event, disability and mortality) were explored. Sensitivity analyses of any association of cerebral small vessel disease at baseline and development of a small arterial occlusion (SAO) were conducted.

Result: Among 12 603 patients with AIS/TIA, median age was 61.7±11.6 years, and 68.2% were men. After adjusting for all potential confounders, frequent-to-severe BG-EPVS was associated with a decreased risk of recurrent ischaemic stroke (HR 0.71, 95% CI 0.55 to 0.92, p=0.01) but an increased risk of haemorrhagic stroke (HR 1.99, 95% CI 1.11 to 3.58, p=0.02) at 1 year after AIS/TIA, compared with none-to-mild BG-EPVS. Patients with frequent-to-severe CSO-EPVS had a decreased risk of disability (OR 0.76, 95% CI 0.62 to 0.92, p=0.004) and all-cause death (HR 0.55, 95% CI 0.31 to 0.98, p=0.04) within 3-month but not 1-year follow-ups, compared with those with none-to-mild BG-EPVS. Sensitivity analyses showed that both BG-EPVS (HR 0.43, 95% CI 0.21 to 0.87, p=0.02) and CSO-EPVS (HR 0.58, 95% CI 0.35 to 0.95, p=0.03) were associated with a decreased risk of subsequent ischaemic stroke in patients with SAO during 1-year follow-up.

Conclusion: BG-EPVS increased the risk of haemorrhagic stroke in patients already with AIS/TIA within 1 year. Therefore, caution is recommended when selecting antithrombotic agents for secondary stroke prevention in patients with AIS/TIA and more severe BG-EPVS.

Background and purpose: To analyse the long-term risk of ischaemic stroke and the clinical effects of antithrombotics on the risk of haemorrhagic stroke in patients with systemic lupus erythematosus (SLE).

Methods: A retrospective cohort study was conducted using a population-based database taken from Taiwan National Health Insurance Research Database. Patients with SLE between 2000 and 2008 were registered and matched with two controls by the index date, age, gender and Charlson Comorbidity Index (CCI). These subjects were followed until either stroke event or 31 December 2013. Adjusted HRs (aHRs) for strokes were estimated with Cox regression models, and the cumulative incidence of ischaemic stroke was analysed by log-rank test and Kaplan-Meier survival analysis.

Results: In total, 8310 patients with SLE and 16 620 patients without SLE were included. In general, patients with SLE had higher rates of ischaemic stroke (5.4% vs 3.3%) and haemorrhagic stroke (1.5% vs 0.6%) than in controls. In multivariate analysis adjusted to age, gender, CCI, urbanisation level and antithrombotics uses, aHRs of all strokes, ischaemic stroke and haemorrhagic stroke were 1.73 (95% CI: 1.54 to 1.94), 1.65 (95% CI: 1.45 to 1.87) and 2.24 (95% CI: 1.71 to 2.95), respectively, in patients with SLE. Patients with SLE were significantly more likely to suffer ischaemic stroke than patients without SLE, even 10 years after SLE diagnosis (6.12% vs 3.50%, p<0.001). Antiplatelet use increased the risk of haemorrhagic stroke in SLE group (aHR=1.74, 95% CI: 1.18 to 2.57).

Conclusions: Patients with SLE are at greater risk of developing ischaemic stroke that lasts for 10 years. Antiplatelets should be carefully administered to prevent cardiovascular events in patients with SLE due to the risk of haemorrhagic stroke.

Background: The superiority of balloon angioplasty plus aggressive medical management (AMM) to AMM alone for symptomatic intracranial artery stenosis (sICAS) on efficacy and safety profiles still lacks evidence from randomised controlled trials (RCTs).

Aim: To demonstrate the design of an RCT on balloon angioplasty plus AMM for sICAS.

Design: Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS) trial is a multicentre, prospective, randomised, open-label, blinded end-point trial to investigate whether balloon angioplasty plus AMM could improve clinical outcome compared with AMM alone in patients with sICAS. Patients eligible in BASIS were 35-80 years old, with a recent transient ischaemic attack within the past 90 days or ischaemic stroke between 14 days and 90 days prior to enrolment due to severe atherosclerotic stenosis (70%-99%) of a major intracranial artery. The eligible patients were randomly assigned to receive balloon angioplasty plus AMM or AMM alone at a 1:1 ratio. Both groups will receive identical AMM, including standard dual antiplatelet therapy for 90 days followed by long-term single antiplatelet therapy, intensive risk factor management and life-style modification. All participants will be followed up for 3 years.

Study outcomes: Stroke or death in the next 30 days after enrolment or after balloon angioplasty procedure of the qualifying lesion during follow-up, or any ischaemic stroke or revascularisation from the qualifying artery after 30 days but before 12 months of enrolment, is the primary outcome.

Discussion: BASIS trail is the first RCT to compare the efficacy and safety of balloon angioplasty plus AMM to AMM alone in sICAS patients, which may provide an alternative perspective for treating sICAS.

Trial registration number: NCT03703635; https://www.

Clinicaltrials: gov.

Background: Unruptured intracranial aneurysm treatment aims to reduce the risk of aneurysm rupture and bleeding, relieves symptoms and improve the quality of life for patients. This study aimed to assess the safety and efficacy of Pipeline Embolization Device (PED, Covidien/Medtronic, Irvine, CA) treatment for intracranial aneurysms presenting with mass effect in real-world settings.

Methods: We selected patients from the PED in China Post-Market Multi-Center Registry Study with mass effect presentation. The study endpoints included postoperative mass effect deterioration and mass effect relief at follow-up (3-36 months). We conducted multivariate analysis to identify factors associated with mass effect relief. Subgroup analyses by aneurysm location, size and form were also performed.

Results: This study included 218 patients with a mean age of 54.3±11.8 years and a female predominance of 74.0% (162/218). The postoperative mass effect deterioration rate was 9.6% (21/218). During a median follow-up period of 8.4 months, the mass effect relief rate was 71.6% (156/218). Notably, immediate aneurysm occlusion following treatment was significantly associated with mass effect relief (OR 0.392, 95% CI, 0.170 to 0.907, p=0.029). Subgroup analysis demonstrated that adjunctive coiling contributed to mass effect relief in cavernous aneurysms, while dense embolism impeded symptom relief in aneurysms<10 mm and saccular aneurysms.

Conclusions: Our data confirmed the efficacy of PED in relieving mass effect. The findings of this study provide support for endovascular treatment to alleviate mass effect in unruptured intracranial aneurysms.

Trial registration number: NCT03831672.

Background: The optimal time to commence anticoagulation in patients with atrial fibrillation (AF) after ischaemic stroke or transient ischaemic attack (TIA) is unclear, with guidelines differing in recommendations. A limitation of previous studies is the focus on clinically overt stroke, rather than radiologically obvious diffusion-weighted imaging ischaemic lesions. We aimed to quantify silent ischaemic lesions and haemorrhages on MRI at 1 month in patients commenced on early (<4 days) vs late (≥4 days) anticoagulation. We hypothesised that there would be fewer ischaemic lesions and more haemorrhages in the early anticoagulant group at 1-month MRI.

Methods: A prospective multicentre, observational cohort study was performed at 11 Australian stroke centres. Clinical and MRI data were collected at baseline and follow-up, with blinded imaging assessment performed by two authors. Timing of commencement of anticoagulation was at the discretion of the treating stroke physician.

Results: We recruited 276 patients of whom 208 met the eligibility criteria. The average age was 74.2 years (SD±10.63), and 79 (38%) patients were female. Median National Institute of Health Stroke Scale score was 5 (IQR 1-12). Median baseline ischaemic lesion volume was 5 mL (IQR 2-17). There were a greater number of new ischaemic lesions on follow-up MRI in patients commenced on anticoagulation ≥4 days after index event (17% vs 8%, p=0.04), but no difference in haemorrhage rates (22% vs 32%, p=0.10). Baseline ischaemic lesion volume of ≤5 mL was less likely to have a new haemorrhage at 1 month (p=0.02). There was no difference in haemorrhage rates in patients with an initial ischaemic lesion volume of >5 mL, regardless of anticoagulation timing.

Conclusion: Commencing anticoagulation <4 days after stroke or TIA is associated with fewer ischaemic lesions at 1 month in AF patients. There is no increased rate of haemorrhage with early anticoagulation. These results suggest that early anticoagulation after mild-to-moderate acute ischaemic stroke associated with AF might be safe, but randomised controlled studies are needed to inform clinical practice.

Background: Given the swift advancements in artificial intelligence (AI), the utilisation of AI-based clinical decision support systems (AI-CDSSs) has become increasingly prevalent in the medical domain, particularly in the management of cerebrovascular disease.

Aims: To describe the design, rationale and methods of a cluster-randomised multifaceted intervention trial aimed at investigating the effect of cerebrovascular disease AI-CDSS on the clinical outcomes of patients who had a stroke and on stroke care quality.

Design: The GOLDEN BRIDGE II trial is a multicentre, open-label, cluster-randomised multifaceted intervention study. A total of 80 hospitals in China were randomly assigned to the AI-CDSS intervention group or the control group. For eligible participants with acute ischaemic stroke in the AI-CDSS intervention group, cerebrovascular disease AI-CDSS will provide AI-assisted imaging analysis, auxiliary stroke aetiology and pathogenesis analysis, and guideline-based treatment recommendations. In the control group, patients will receive the usual care. The primary outcome is the occurrence of new vascular events (composite of ischaemic stroke, haemorrhagic stroke, myocardial infarction or vascular death) at 3 months after stroke onset. The sample size was estimated to be 21 689 with a 26% relative reduction in the incidence of new composite vascular events at 3 months by using multiple quality-improving interventions provided by AI-CDSS. All analyses will be performed according to the intention-to-treat principle and accounted for clustering using generalised estimating equations.

Conclusions: Once the effectiveness is verified, the cerebrovascular disease AI-CDSS could improve stroke care and outcomes in China.

Trial registration number: NCT04524624.

Background: The Catfish stent retriever is a newly developed mechanical thrombectomy device for rapid recanalisation in emergent large vessel occlusion (ELVO) stroke. The current trial aimed to assess whether the Catfish stent retriever is non-inferior to the Solitaire stent retriever in terms of outcomes in ELVO stroke.

Methods: This was a randomised, prospective, parallel-group, multicentre, open-label, non-inferiority study conducted at 18 sites in China. The primary outcome was the proportion of cases with successful recanalisation (modified thrombolysis in cerebral infarction score of 2b or 3) following the procedure. Secondary efficacy outcomes included the National Institutes of Health Stroke Scale scores at 24 hours and 7 days or discharge if earlier, time from artery puncture to successful recanalisation and good clinical outcome (modified Rankin scale score ≤2) at 90 days. Safety outcomes included symptomatic intracranial haemorrhage, all cause-death and severe adverse events at 90 days.

Results: Between 3 March 2019 and 5 June 2021, 118 and 120 patients were randomly allocated to the Catfish and Solitaire groups, respectively. The primary endpoint after all endovascular procedures was non-inferior in the Catfish group (88.5%, 100/113) than in the Solitaire group (87.7%, 100/114), with a rate difference (RD) of 0.78% (95% CI -7.64 to -9.20; p=0.001). Sensitivity analysis only considering the per-protocol set also yielded similar results, with an RD of 0.83% (95% CI -7.03 to -8.70; p<0.001). Additionally, the proportions of cases with good clinical outcomes (47.8% vs 50.0%, p=0.739) and all-cause death rates (17.7% vs 18.8%, p=0.700) were similar in both groups at 90 days.

Conclusions: The Catfish stent retriever is an effective and safe device for endovascular recanalisation in ELVO stroke.

Trial registration number: NCT03820882.