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).
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.
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).
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.
It remains unclear whether enlarged perivascular spaces (EPVS) predict poor clinical outcomes in patients with acute ischaemic stroke (AIS) or transient ischaemic attack (TIA).
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.
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.
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.
Craniocervical junction (CCJ) arteriovenous fistulas (AVFs) are rare. The current treatment strategies for AVFs with different angioarchitecture need to be clarified. The present study aimed to analyse the correlation between angioarchitecture and clinical characteristics, share our experience in treating this disease and identify risk factors associated with subarachnoid haemorrhage (SAH) and poor outcomes.
A total of 198 consecutive patients with CCJ AVFs from our neurosurgical centre were retrospectively reviewed. The patients were grouped according to their clinical manifestations, and their baseline clinical characteristics, angioarchitecture, treatment strategies and outcomes were summarised.
The patients’ median age was 56 years (IQR 47–62 years). The majority of patients were men with 166 (83.8%) patients. The most common clinical manifestation was SAH (52.0%), followed by venous hypertensive myelopathy (VHM) (45.5%). The most common CCJ AVFs type was dural AVF, with 132 (63.5%) fistulas. The most frequent fistula location was C-1 (68.7%) and dural branch of vertebral artery (70.2%) was the most involved arterial feeders for fistulas. The most common direction of venous drainage was descending intradural drainage (40.9%), followed by ascending intradural drainage (36.5%). Microsurgery was the most common treatment strategy applied for 151 (76.3%) patients, 15 (7.6%) patients were treated with interventional embolisation only, and 27 (13.6%) received both interventional embolisation and microsurgical treatment. The learning curve for microsurgery only was analysed by cumulative summation method, and the turning point was the 70th case, and blood loss in post-group was lower than that in pre-group (p=0.034). At the last follow-up, there were 155 (78.3%) patients with favourable outcomes (modified Rankin Scale(mRS)<3). Age≥56 (OR 2.038, 95% CI 1.039 to 3.998, p=0.038), VHM as the clinical manifestation (OR 4.102, 95% CI 2.108 to 7.982, p<0.001) and pretreatment mRS≥3 (OR 3.127, 95% CI 1.617 to 6.047, p<0.001) were significantly associated with poor outcomes.
The arterial feeders and direction of the venous drainage were important factors in the clinical presentations. The location of fistula and drainage vein was essential for choosing different treatment strategies. Older age, VHM onset and poor pretreatment functional status predicted poor outcomes.
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.
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.
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.
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.
The effect of transdermal glyceryl trinitrate (GTN, a nitrovasodilator) on clinical outcome when administered before hospital admission in suspected stroke patients is unclear. Here, we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2).
RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4 hours of onset. The primary outcome was a shift in scores on the modified Rankin scale (mRS) at day 90. Secondary outcomes included death; a global analysis (Wei-Lachin test) containing Barthel Index, EuroQol-5D, mRS, telephone interview for cognitive status-modified and Zung depression scale; and neuroimaging-determined ‘brain frailty’ markers. Data were reported as n (%), mean (SD), median [IQR], adjusted common OR (acOR), mean difference or Mann-Whitney difference (MWD) with 95% CI.
597 of 1149 (52%) patients had a final diagnosis of ischaemic stroke; age 75 (12) years, premorbid mRS>2 107 (18%), Glasgow Coma Scale 14 (2) and time from onset to randomisation 67 [45, 108] min. Neuroimaging ‘brain frailty’ was common: median score 2 [2, 3] (range 0–3). At day 90, GTN did not influence the primary outcome (acOR for increased disability 1.15, 95% CI 0.85 to 1.54), death or global analysis (MWD 0.00, 95% CI –0.10 to 0.09). In subgroup analyses, there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1 hour of symptom onset and in those with more severe stroke.
In patients who had an ischaemic stroke, ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital trials.
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.
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.
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.
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.
Our recent pilot study suggests intra-arterial tenecteplase (TNK) during the first pass of endovascular treatment (EVT) seems safe, may increase first-pass reperfusion and good outcome in acute ischaemic stroke (AIS) patients with large-vessel occlusion (LVO).
To determine the efficacy and safety of intra-arterial TNK administration during EVT in AIS-LVO patients presenting up to 24 hours from symptom onset.
A maximum of 380 patients are required to test the superiority hypothesis with 80% power according to a two-side 0.05 level of significance, stratified by age, gender, baseline systolic blood pressure, prestroke modified Rankin Scale (mRS), baseline National Institute of Health stroke scale, baseline ASPECTS, time from onset to groin puncture, intravenous thrombolysis before EVT, stroke territory and stroke aetiology.
Intra-arterial TNK during thrombectomy for acute stroke (BRETIS-TNK II) study is a prospective, randomised, adaptive enrichment, open-label, blinded end point, multicentre study. Eligible AIS-LVO patients are randomly assigned into the experimental group and control group with a ratio of 1:1. The experimental group will be treated with intra-arterial infusion of TNK during EVT. The control group will be treated with standard EVT.
The primary end point is a favourable outcome, defined as an mRS score of 0–2 at 90 days. The primary safety end point is symptomatic intracranial haemorrhage within 48 hours, which is defined as an increase in the National Institutes of Health Stroke Scale score of ≥4 points as a result of the intracranial haemorrhage.
The results of BRETIS-TNK II will provide evidence for the efficacy and safety of intra-arterial TNK administration during EVT in AIS patients with LVO.
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).
To demonstrate the design of an RCT on balloon angioplasty plus AMM for sICAS.
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.
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.
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.
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.
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.
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.
The STRATEGY trial will assess whether tirofiban combined with aspirin is effective and safe in preventing recurrence and END in patients with PAI.
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.
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.
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.
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.
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.
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.
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.
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.
China is one of the countries with the highest burden of stroke. Implementing multidimensional management guidelines will help clinicians practise evidence-based care, improve patient outcomes and alleviate societal burdens. This update of the 2019 edition will provide the latest comprehensive recommendations for the diagnosis and treatment of ischaemic cerebrovascular diseases.
We conducted a comprehensive search on MEDLINE (via PubMed) up to 31 August 2023. The writing team established the recommendations through multiple rounds of online and offline discussions. Each recommendation was graded using the evidence grading algorithm developed by the Chinese Stroke Association (CSA). The draft was reviewed and finalised by the CSA Stroke Guidelines Writing Committee.
This update included revisions of 15 existing recommendations and 136 new recommendations in the following areas of stroke care: emergency assessment and diagnosis of ischaemic cerebrovascular disease, acute-phase reperfusion therapy, evaluation of underlying mechanisms, antithrombotic therapy, prevention and treatment of complications, and risk factor management.
This guideline updated the recommendations for the clinical management of ischaemic cerebrovascular disease from 2019.
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.
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.
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.
The Catfish stent retriever is an effective and safe device for endovascular recanalisation in ELVO stroke.
Small subcortical infarcts account for up to 25% of ischaemic strokes. Thalamus is one of the subcortical structures that commonly manifest with lacunar infarcts on MRI of the brain. Studies have shown that thalamus infarction is associated with cognitive decline. However, due to the lack of proper animal models, little is known about the mechanism. We aimed to establish a focal thalamus infarction model, characterise the infarct lesion and assess functional effects.
Male C57BL/6J mice were anaesthetised, and Rose Bengal dye was injected through the tail vein. The right thalamus was illuminated with green laser light by stereotactic implantation of optic fibre. Characteristics of the infarct and lesion evolution were evaluated by histological analysis and 7T MRI at various times. The cognitive and neurological functions were assessed by behavioural tests. Retrograde tracing was performed to analyse neural connections.
An ischaemic lesion with small vessel occlusion was observed in the thalamus. It became a small circumscribed infarct with reactive astrocytes accumulated in the infarct periphery on day 21. The mice with thalamic infarction demonstrated impaired learning and memory without significant neurological deficits. Retrogradely labelled neurons in the retrosplenial granular cortex were reduced.
This study established a mouse model of thalamic lacunar infarction that exhibits cognitive impairment. Neural connection dysfunctions may play a potential role in post-stroke cognitive impairment. This model helps to clarify the pathophysiology of post-stroke cognitive impairment and to develop potential therapies.
Extra-axial cavernous hemangiomas (ECHs) are sporadic and rare intracranial occupational lesions that usually occur within the cavernous sinus. The aetiology of ECHs remains unknown.
Whole-exome sequencing was performed on ECH lesions from 12 patients (discovery cohort) and droplet digital polymerase-chain-reaction (ddPCR) was used to confirm the identified mutation in 46 additional cases (validation cohort). Laser capture microdissection (LCM) was carried out to capture and characterise subgroups of tissue cells. Mechanistic and functional investigations were carried out in human umbilical vein endothelial cells and a newly established mouse model.
We detected somatic GJA4 mutation (c.121G>T, p.G41C) in 5/12 patients with ECH in the discovery cohort and confirmed the finding in the validation cohort (16/46). LCM followed by ddPCR revealed that the mutation was enriched in lesional endothelium. In vitro experiments in endothelial cells demonstrated that the GJA4 mutation activated SGK-1 signalling that in turn upregulated key genes involved in cell hyperproliferation and the loss of arterial specification. Compared with wild-type littermates, mice overexpressing the GJA4 mutation developed ECH-like pathological morphological characteristics (dilated venous lumen and elevated vascular density) in the retinal superficial vascular plexus at the postnatal 3 weeks, which were reversed by an SGK1 inhibitor, EMD638683.
We identified a somatic GJA4 mutation that presents in over one-third of ECH lesions and proposed that ECHs are vascular malformations due to GJA4-induced activation of the SGK1 signalling pathway in brain endothelial cells.
Poststroke depression and anxiety, independent predictor of poor functional outcomes, are common in the acute phase of stroke. Up to now, there is no fast-onset antidepressive and anxiolytic agents suitable for the management of acute stroke. ZL006-05, a dual-target analgesic we developed, dissociates nitric oxide synthase from postsynaptic density-95 while potentiates α2-containing -aminobutyric acid type A receptor. This study aims to determine whether ZL006-05 can be used as an antistroke agent with fast-onset antidepressant and anxiolytic effects.
Photothrombotic stroke and transient middle cerebral artery occlusion were induced in rats and mice. Infarct size was measured by TTC(2,3,5-Triphenyltetrazolium chloride) staining or Nissl staining. Neurological defects were assessed by four-point scale neurological score or modified Neurological Severity Scores. Grid-walking, cylinder and modified adhesive removal tasks were conducted to assess sensorimotor functions. Spatial learning was assessed using Morris water maze task. Depression and anxiety were induced by unpredictable chronic mild stress. Depressive behaviours were assessed by tail suspension, forced swim and sucrose preference tests. Anxiety behaviours were assessed by novelty-suppressed feeding and elevated plus maze tests. Pharmacokinetics, toxicokinetics and long-term toxicity studies were performed in rats.
Administration of ZL006-05 in the acute phase of stroke attenuated transient and permanent ischaemic injury and ameliorated long-term functional impairments significantly, with a treatment window of 12 hours after ischemia, and reduced plasminogen activato-induced haemorrhagic transformation. ZL006-05 produced fast-onset antidepressant and anxiolytic effects with onset latency of 1 hour in the normal and CMS mice, had antidepressant and anxiolytic effects in stroke mice. ZL006-05 crossed the blood–brain barrier and distributed into the brain rapidly, and had a high safety profile in toxicokinetics and long-term toxicological studies.
ZL006-05 is a new neuroprotectant with fast-onset antidepressant and anxiolytic effects and has translational properties in terms of efficacy, safety and targeting of clinical issues.
Previous prediction algorithms for cardiovascular diseases (CVD) were established using risk factors retrieved largely based on empirical clinical knowledge. This study sought to identify predictors among a comprehensive variable space, and then employ machine learning (ML) algorithms to develop a novel CVD risk prediction model.
From a longitudinal population-based cohort of UK Biobank, this study included 473 611 CVD-free participants aged between 37 and 73 years old. We implemented an ML-based data-driven pipeline to identify predictors from 645 candidate variables covering a comprehensive range of health-related factors and assessed multiple ML classifiers to establish a risk prediction model on 10-year incident CVD. The model was validated through a leave-one-center-out cross-validation.
During a median follow-up of 12.2 years, 31 466 participants developed CVD within 10 years after baseline visits. A novel UK Biobank CVD risk prediction (UKCRP) model was established that comprised 10 predictors including age, sex, medication of cholesterol and blood pressure, cholesterol ratio (total/high-density lipoprotein), systolic blood pressure, previous angina or heart disease, number of medications taken, cystatin C, chest pain and pack-years of smoking. Our model obtained satisfied discriminative performance with an area under the receiver operating characteristic curve (AUC) of 0.762±0.010 that outperformed multiple existing clinical models, and it was well-calibrated with a Brier Score of 0.057±0.006. Further, the UKCRP can obtain comparable performance for myocardial infarction (AUC 0.774±0.011) and ischaemic stroke (AUC 0.730±0.020), but inferior performance for haemorrhagic stroke (AUC 0.644±0.026).
ML-based classification models can learn expressive representations from potential high-risked CVD participants who may benefit from earlier clinical decisions.
Inflammation-exacerbated secondary brain injury and limited tissue regeneration are barriers to favourable prognosis after intracerebral haemorrhage (ICH). As a regulator of inflammation and lipid metabolism, Liver X receptor (LXR) has the potential to alter microglia/macrophage (M/M) phenotype, and assist tissue repair by promoting cholesterol efflux and recycling from phagocytes. To support potential clinical translation, the benefits of enhanced LXR signalling are examined in experimental ICH.
Collagenase-induced ICH mice were treated with the LXR agonist GW3965 or vehicle. Behavioural tests were conducted at multiple time points. Lesion and haematoma volume, and other brain parameters were assessed using multimodal MRI with T2-weighted, diffusion tensor imaging and dynamic contrast-enhanced MRI sequences. The fixed brain cryosections were stained and confocal microscopy was applied to detect LXR downstream genes, M/M phenotype, lipid/cholesterol-laden phagocytes, oligodendrocyte lineage cells and neural stem cells. Western blot and real-time qPCR were also used. CX3CR1CreER: Rosa26iDTR mice were employed for M/M-depletion experiments.
GW3965 treatment reduced lesion volume and white matter injury, and promoted haematoma clearance. Treated mice upregulated LXR downstream genes including ABCA1 and Apolipoprotein E, and had reduced density of M/M that apparently shifted from proinflammatory interleukin-1β+ to Arginase1+CD206+ regulatory phenotype. Fewer cholesterol crystal or myelin debris-laden phagocytes were observed in GW3965 mice. LXR activation increased the number of Olig2+PDGFRα+ precursors and Olig2+CC1+ mature oligodendrocytes in perihaematomal regions, and elevated SOX2+ or nestin+ neural stem cells in lesion and subventricular zone. MRI results supported better lesion recovery by GW3965, and this was corroborated by return to pre-ICH values of functional rotarod activity. The therapeutic effects of GW3965 were abrogated by M/M depletion in CX3CR1CreER: Rosa26iDTR mice.
LXR agonism using GW3965 reduced brain injury, promoted beneficial properties of M/M and facilitated tissue repair correspondent with enhanced cholesterol recycling.
The ring finger protein 213 gene (RNF213) p.R4810K variant increased the risk of acute ischaemic stroke (AIS) attributable to intracranial arterial stenosis (ICAS) in the Japanese and Korean populations. In this study, we aimed to examine the prevalence of the RNF213 p.R4810K variant in Chinese patients with AIS or transient ischaemic attack and identify the phenotype of the carriers.
We analysed data from the Third China National Stroke Registry. All included participants were divided into two groups by carrier status of the p.R4810K variant. The aetiological classification was conducted according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. The presence of ICAS and extracranial arterial stenosis (ECAS) was defined as 50%–99% stenosis or occlusion of any intracranial and extracranial artery. Logistic regression models and Cox regression models were used to evaluate the association of the p.R4810K variant with TOAST classification, stenosis phenotypes and clinical outcomes.
A total of 10 381 patients were enrolled, among which 56 (0.5%) had the heterozygote GA genotype for p.R4810K. The variant carriers were younger (p=0.01), and more likely to suffer from peripheral vascular disease (p=0.04). The p.R4810K variant was associated with large-artery atherosclerosis (LAA) (adjusted OR=1.94, 95% CI 1.13 to 3.33), anterior circulation stenosis (adjusted OR=2.12, 95% CI 1.23 to 3.65) and ECAS (adjusted OR=2.29, 95% CI 1.16 to 4.51). Nevertheless, the p.R4810K variant was not associated with recurrence, poor functional outcome and mortality at 3 months and 1 year.
The RNF213 p.R4810K variant was associated with LAA, anterior circulation stenosis and ECAS in Chinese patients. Given the low carrying rate and only 1-year follow-up information, caution should be taken to interpret our findings in no statistically significant association between the p.R4810K variant and stroke prognosis in Chinese patients.
Prestroke physical activity (PA) has been linked to improved outcomes after intracerebral haemorrhage (ICH), but its association with ICH volume is unknown. We aimed to investigate associations of prestroke PA with location-specific haematoma volume and the clinical outcome of ICH.
All patients with primary ICH, admitted to three hospitals between 2014 and 2019, were included. Patients performing light PA ≥4 hour/week the year before stroke were considered physically active. Haematoma volumes were assessed from admission brain imaging. Adjusted associations were estimated using multivariate linear and logistic regression models. Haematoma volume was explored as mediator to the relationship between prestroke PA and mild stroke severity (0–4 points on the National Institutes of Health Stroke Scale), a good 1-week functional status (0–3 points on the modified Rankin Scale) and 90-day survival. Average direct effects (ADE) and average causal mediation effects (ACME) were computed.
Of 686 primary ICH cases, 349 were deep, 240 lobar and 97 infratentorial. Prestroke PA predicted smaller haematoma volumes in deep ICH (β=–0.36, SE=0.09, p<0.001) and lobar ICH (β=–0.23, SE=0.09, p=0.016). Prestroke PA was also associated with mild stroke severity (OR 2.53, 95% CI 1.59 to 4.01), a good 1-week functional status (OR 2.12, 95% CI 1.37 to 3.30) and 90-day survival (OR 3.48, 95% CI 2.06 to 5.91). Haematoma volume partly mediated the relationships between PA and stroke severity (ADE 0.08, p=0.004; ACME 0.10, p<0.001), 1-week functional status (ADE 0.07, p=0.03; ACME 0.10, p<0.001) and 90-day survival (ADE 0.14, p<0.001; ACME 0.05, p<0.001).
Light PA ≥4 hour/week prior to ICH was associated with smaller haematoma volumes in deep and lobar locations. Physically active patients with ICH had a higher likelihood of mild stroke, a good 1-week functional status and 90-day survival, in part mediated by smaller haematoma volumes on admission.
We aimed to investigate the white matter (WM) microstructural/cytostructural disintegrity patterns related to higher systolic blood pressure (SBP), and whether they mediate SBP effects on cognitive performance in middle-aged adults.
Using the UK Biobank study of community-dwelling volunteers aged 40–69 years, we included participants without a history of stroke, dementia, demyelinating disease or traumatic brain injury. We investigated the association of SBP with MRI diffusion metrics: fractional anisotropy (FA), mean diffusivity (MD), intracellular volume fraction (a measure of neurite density), isotropic (free) water volume fraction (ISOVF) and orientation dispersion across WM tracts. Then, we determined whether WM diffusion metrics mediated the effects of SBP on cognitive function.
We analysed 31 363 participants—mean age of 63.8 years (SD: 7.7), and 16 523 (53%) females. Higher SBP was associated with lower FA and neurite density, but higher MD and ISOVF. Among different WM tracts, diffusion metrics of the internal capsule anterior limb, external capsule, superior and posterior corona radiata were most affected by higher SBP. Among seven cognitive metrics, SBP levels were only associated with ‘fluid intelligence’ (adjusted p<0.001). In mediation analysis, the averaged FA of external capsule, internal capsule anterior limb and superior cerebellar peduncle mediated 13%, 9% and 13% of SBP effects on fluid intelligence, while the averaged MD of external capsule, internal capsule anterior and posterior limbs, and superior corona radiata mediated 5%, 7%, 7% and 6% of SBP effects on fluid intelligence, respectively.
Among asymptomatic adults, higher SBP is associated with pervasive WM microstructure disintegrity, partially due to reduced neuronal count, which appears to mediate SBP adverse effects on fluid intelligence. Diffusion metrics of select WM tracts, which are most reflective of SBP-related parenchymal damage and cognitive impairment, may serve as imaging biomarkers to assess treatment response in antihypertensive trials.
Deep brain stimulation (DBS) has been preliminarily applied to treat patients with disorders of consciousness (DoCs). The study aimed to determine whether DBS was effective for treating patients with DoC and identify factors related to patients’ outcomes.
Data from 365 patients with DoCs who were consecutively admitted from 15 July 2011 to 31 December 2021 were retrospectively analysed. Multivariate regression and subgroup analysis were performed to adjust for potential confounders. The primary outcome was improvement in consciousness at 1 year.
An overall improvement in consciousness at 1 year was achieved in 32.4% (12/37) of the DBS group compared with 4.3% (14/328) of the conservative group. After full adjustment, DBS significantly improved consciousness at 1 year (adjusted OR 11.90, 95% CI 3.65–38.46, p<0.001). There was a significant treatmentxfollow up interaction (H=14.99, p<0.001). DBS had significantly better effects in patients with minimally conscious state (MCS) compared with patients with vegetative state/unresponsive wakefulness syndrome (p for interaction <0.001). A nomogram based on age, state of consciousness, pathogeny and duration of DoCs indicated excellent predictive performance (c-index=0.882).
DBS was associated with better outcomes in patients with DoC, and the effect was likely to be significantly greater in patients with MCS. DBS should be cautiously evaluated by nomogram preoperatively, and randomised controlled trials are still needed.
Retinal pathologies are an independent risk factor for ischaemic stroke, but research on the predictive value of retinal abnormalities for recurrent vascular events in patients with prior stroke is inconclusive. We investigated the association of retinal pathologies with subsequent vascular events.
In a substudy of the Intensified secondary prevention intending a reduction of recurrent events in TIA and minor stroke patients (INSPiRE-TMS) trial, we enrolled patients with recent transient ischaemic attack (TIA) or minor stroke with at least one modifiable risk factor. Primary outcome was the composite of subsequent vascular events. Retinal photographs were taken at baseline and categorised into three different fundus groups by a telemedically linked ophthalmologist.
722 patients participated in the current study and 109 major vascular events occurred. After multivariable adjustments, we did not find a significant association between fundus categories and risk for subsequent vascular events (HRs for moderate vascular retinopathy and vascular retinopathy with vessel rarefaction in comparison to no vascular retinopathy 1.03 (95% CI 0.64 to 1.67), p=0.905 and 1.17 (95% CI 0.62 to 2.20), p=0.626). In a selective post hoc analysis in patients with diabetes mellitus and hypertension, patients with vascular retinopathy with vessel rarefaction had a higher risk for recurrent stroke (HR 24.14 (95% CI 2.74 to 212.50), p=0.004).
Retinal changes did not predict major subsequent vascular events in patients with recent TIA or minor stroke. Further studies are needed to examine the utility of fundus photography in assessing the risk of stroke recurrence in patients with diabetes mellitus and hypertension.
To determine the characteristics of intracranial plaque proximal to large vessel occlusion (LVO) in stroke patients without major-risk cardioembolic source using 3.0 T high-resolution MRI (HR-MRI).
We retrospectively enrolled eligible patients from January 2015 to July 2021. The multidimensional parameters of plaque such as remodelling index (RI), plaque burden (PB), percentage lipid-rich necrotic core (%LRNC), presence of discontinuity of plaque surface (DPS), fibrous cap rupture, intraplaque haemorrhage and complicated plaque were evaluated by HR-MRI.
Among 279 stroke patients, intracranial plaque proximal to LVO was more prevalent in the ipsilateral versus contralateral side to stroke (75.6% vs 58.8%, p<0.001). The larger PB (p<0.001), RI (p<0.001) and %LRNC (p=0.001), the higher prevalence of DPS (61.1% vs 50.6%, p=0.041) and complicated plaque (63.0% vs 50.6%, p=0.016) were observed in the plaque ipsilateral versus contralateral to stroke. Logistic analysis showed that RI and PB were positively associated with an ischaemic stroke (RI: crude OR: 1.303, 95% CI 1.072 to 1.584, p=0.008; PB: crude OR: 1.677, 95% CI 1.381 to 2.037, p<0.001). In subgroup with <50% stenotic plaque, the greater PB, RI, %LRNC and the presence of complicated plaque were more closely related to stroke, which was not evident in subgroup with ≥50% stenotic plaque.
This is the first study to report the characteristics of intracranial plaque proximal to LVO in non-cardioembolic stroke. It provides potential evidence to support different aetiological roles of <50% stenotic vs ≥50% stenotic intracranial plaque in this population.
In-stent restenosis (ISR) belongs to an infrequent but potentially serious complication after carotid angioplasty and stenting in patients with severe carotid stenosis. Some of these patients might be contraindicated to repeat percutaneous transluminal angioplasty with or without stenting (rePTA/S). The purpose of the study is to compare the safety and effectiveness of carotid endarterectomy with stent removal (CEASR) and rePTA/S in patients with carotid ISR.
Consecutive patients with carotid ISR (≥80%) were randomly allocated to the CEASR or rePTA/S group. The incidence of restenosis after intervention, stroke, transient ischaemic attack myocardial infarction and death 30 days and 1 year after intervention and restenosis 1 year after intervention between patients in CEASR and rePTA/S groups were statistically evaluated.
A total of 31 patients were included in the study; 14 patients (9 males; mean age 66.3±6.6 years) were allocated to CEASR and 17 patients (10 males; mean age 68.8±5.6 years) to the rePTA/S group. The implanted stent in carotid restenosis was successfully removed in all patients in the CEASR group. No clinical vascular event was recorded periproceduraly, 30 days and 1 year after intervention in both groups. Only one patient in the CEASR group had asymptomatic occlusion of the intervened carotid artery within 30 days and one patient died in the rePTA/S group within 1 year after intervention. Restenosis after intervention was significantly greater in the rePTA/S group (mean 20.9%) than in the CEASR group (mean 0%, p=0.04), but all stenoses were <50%. Incidence of 1-year restenosis that was ≥70% did not differ between the rePTA/S and CEASR groups (4 vs 1 patient; p=0.233).
CEASR seems to be effective and save procedures for patients with carotid ISR and might be considered as a treatment option.
The timing for initiating anticoagulant therapy in acute ischaemic stroke (AIS) patients with atrial fibrillation who recanalised after endovascular treatment (EVT) is unclear. The objective of this study was to evaluate the effect of early anticoagulation after successful recanalisation in AIS patients with atrial fibrillation.
Patients with anterior circulation large vessel occlusion and atrial fibrillation who were successfully recanalised by EVT within 24 hours after stroke in the Registration Study for Critical Care of Acute Ischemic Stroke after Recanalization registry were analysed. Early anticoagulation was defined as the initiation of unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) within 72 hours after EVT. Ultra-early anticoagulation was defined if it was initiated within 24 hours. The primary efficacy outcome was the score on the modified Rankin Scale (mRS) at day 90, and the primary safety outcome was symptomatic intracranial haemorrhage within 90 days.
Overall, 257 patients were enrolled, of whom 141 (54.9%) initiated anticoagulation within 72 hours after EVT, including 111 within 24 hours. A significant shift towards better mRS scores at day 90 was associated with early anticoagulation (adjusted common OR 2.08 (95% CI 1.27 to 3.41)). Symptomatic intracranial haemorrhage was comparable between patients treated with early and routine anticoagulation (adjusted OR 0.20 (95% CI 0.02 to 2.18)). Comparison of different early anticoagulation regimens showed that ultra-early anticoagulation was more significantly associated with favourable functional outcomes (adjusted common OR 2.03 (95% CI 1.20 to 3.44)) and reduced the incidence of asymptomatic intracranial haemorrhage (OR 0.37 (95% CI 0.14 to 0.94)).
In AIS patients with atrial fibrillation, early anticoagulation with UFH or LMWH after successful recanalisation is associated with favourable functional outcomes without increasing the risk of symptomatic intracranial haemorrhages.
ChiCTR1900022154.
Acute brain ischaemia elicits pronounced inflammation, which aggravates neural injury. However, the mechanisms governing the resolution of acute neuroinflammation remain poorly understood. In contrast to regulatory T and B cells, group 2 innate lymphoid cells (ILC2s) are immunoregulatory cells that can be swiftly mobilised without antigen presentation; whether and how these ILC2s participate in central nervous system inflammation following brain ischaemia is still unknown.
Leveraging brain tissues from patients who had an ischaemic stroke and a mouse model of focal ischaemia, we characterised the presence and cytokine release of brain-infiltrating ILC2s. The impact of ILC2s on neural injury was evaluated through antibody depletion and ILC2 adoptive transfer experiments. Using Rag2–/–c–/– mice receiving passive transfer of IL-4–/– ILC2s, we further assessed the contribution of interleukin (IL)-4, produced by ILC2s, in ischaemic brain injury.
We demonstrate that ILC2s accumulate in the areas surrounding the infarct in brain tissues of patients with cerebral ischaemia, as well as in mice subjected to focal cerebral ischaemia. Oligodendrocytes were a major source of IL-33, which contributed to ILC2s mobilisation. Adoptive transfer and expansion of ILC2s reduced brain infarction. Importantly, brain-infiltrating ILC2s reduced the magnitude of stroke injury severity through the production of IL-4.
Our findings revealed that brain ischaemia mobilises ILC2s to curb neuroinflammation and brain injury, expanding the current understanding of inflammatory networks following stroke.
This study aims to investigate the associations of glymphatic system with the presence, severity and neuroimaging phenotypes of cerebral small vessel disease (CSVD) in a community-based population.
This report included 2219 community-dwelling people aged 50–75 years who participated in the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events cohort. The diffusivity along perivascular spaces based on diffusion tensor imaging (DTI-ALPS index) was measured to assess glymphatic pathway. The presence and severity of CSVD were estimated using a CSVD score (points from 0 to 6) and a modified CSVD score (points from 0 to 4), which were driven by 4 neuroimaging features of CSVD, including white matter hyperintensity (WMH), enlarged perivascular spaces (EPVS), lacunes, cerebral microbleeds. Brain atrophy (BA) was also evaluated. Binary or ordinal logistic regression analyses were carried out to investigate the relationships of DTI-ALPS index with CSVD.
The mean age was 61.3 (SD 6.6) years, and 1019 (45.9%) participants were men. The average DTI-ALPS index was 1.67±0.14. Individuals in the first quartile (Q1) of the DTI-ALPS index had higher risks of the presence of CSVD (OR 1.77, 95% CI 1.33 to 2.35, p<0.001), modified presence of CSVD (odds ratio (OR) 1.80, 95% CI 1.38 to 2.34, p<0.001), total burden of CSVD (common OR (cOR) 1.89, 95% CI 1.43 to 2.49, p<0.001) and modified total burden of CSVD (cOR 1.95, 95% CI 1.51 to 2.50, p<0.001) compared with those in the fourth quartile (Q4). Additionally, individuals in Q1 of the DTI-ALPS index had increased risks of WMH burden, modified WMH burden, lacunes, basal ganglia-EPVS and BA (all p<0.05).
A lower DTI-ALPS index underlay the presence, severity and typical neuroimaging markers of CSVD, implying that glymphatic impairment may interact with CSVD-related pathology in the general ageing population.
Cerebrovascular parenchymal damage is prevalent in ageing brains; however, its vascular aetiology has not been fully elucidated. In addition to the underlying role of sclerotic arterioles, the correlation between collagenised venules has not been clarified. Here, we aimed to investigate the associations between microvascular injuries, including arteriolosclerosis and venular collagenosis, and related parenchymal damages in ageing brains, to investigate the underlying correlations.
We evaluated arteriolosclerosis and venular collagenosis in 7 regions from 27 autopsy cases with no history of stroke or brain tumour. The correlations between the ratio of arteriolosclerosis, venular collagenosis and the severity of cerebrovascular parenchymal damage, including lacunes, microinfarcts, myelin loss, and parenchymal and perivascular haemosiderin deposits, were assessed.
Arteriolosclerosis and venular collagenosis became more evident with age. Arteriolosclerosis was associated with lacunes (p=0.004) and brain parenchymal haemosiderin deposits in the superior frontal cortex (p=0.024) but not with leukoaraiosis severity. Venular collagenosis was not associated with the number of lacunes or haemosiderin, while white matter generally became paler with severe venular collagenosis in the periventricular (β=–0.430, p=0.028) and deep white matter (β=–0.437, p=0.025).
Our findings imply an important role for venular lesions in relation to microvessel-related parenchymal damage which is different from that for arteriolosclerosis. Different underlying mechanisms of both cerebral arterioles and venules require further investigation.
Knowledge regarding the pharmacological treatment for moyamoya disease (MMD), a chronic and progressive cerebrovascular disease conferring greater stroke risk, is limited. In the present study, whether statin therapy is associated with a reduced risk of stroke in patients with MMD was investigated.
This was a retrospective cohort study in which the occurrence of stroke in patients with newly diagnosed MMD was investigated using the nationwide health insurance database in Korea from January 2007 to March 2021. A multivariable Cox proportional hazards regression model was constructed for stroke, in which statin therapy after MMD diagnosis was treated as a time-dependent variable. Adjustment was done for sex, age, presence of comorbidities, concurrent stroke, revascularisation surgery and treatment with antiplatelets.
The present study included 13 373 newly diagnosed patients with MMD; 40.8% had a concurrent stroke at the time of MMD diagnosis. During the mean follow-up of 5.1±3.3 years, 631 patients (4.7%) suffered a stroke event (haemorrhagic stroke: 458 patients, ischaemic stroke: 173 patients). Statin therapy after MMD diagnosis was significantly associated with a reduced risk of stroke (adjusted HR 0.74; 95% CI 0.60 to 0.91, p=0.004). In the secondary outcome analysis, the risk of haemorrhagic stroke (adjusted HR 0.74; 95% CI 0.58 to 0.95, p=0.018) and ischaemic stroke (adjusted HR 0.75; 95% CI 0.52 to 1.08, p=0.124) were reduced with the statin treatment. Taking statins was also associated with a lower risk of all-cause mortality (adjusted HR 0.47; 95% CI 0.33 to 0.67, p<0.001).
In patients with MMD, statin therapy was associated with a reduced risk of subsequent stroke. The findings indicate statin treatment may be beneficial for patients with MMD, however the results should be confirmed in randomised controlled trials.
Atherosclerosis is a very complex process influenced by various systemic and local factors. Therefore, in patients with bilateral carotid plaques (BCPs), there may be differences in carotid plaque vulnerability between the sides. We aimed to investigate the differences in BCP characteristics in patients with BCPs using magnetic resonance vessel wall imaging (MR-VWI).
Participants with BCPs were selected for subanalysis from a multicentre study of Chinese Atherosclerosis Risk Evaluation II. We measured carotid plaque burden, identified each plaque component and measured their volume or area bilaterally on MR-VWI. Paired comparisons of the burden and components of BCPs were performed.
In all, 540 patients with BCPs were eligible for analysis. Compared with the right carotid artery (CA), larger mean lumen area (p<0.001), larger mean wall area (p=0.025), larger mean total vessel area (p<0.001) and smaller normalised wall index (p=0.006) were found in the left CA. Regarding plaque components, only the prevalence of lipid-rich necrotic core (LRNC) in the left CA was higher (p=0.026). For patients with a vulnerable plaque component coexisting on both sides, only the intraplaque haemorrhage (IPH) volume (p=0.011) was significantly greater in the left CA than in the right CA.
There were asymmetries in plaque growth and evolution between BCPs. The left carotid plaques were more likely to have larger plaque burden, higher prevalence of LRNC and greater IPH volume, which may contribute to the lateralisation of ischaemic stroke in the cerebral hemispheres.
Pial arteriovenous fistulas (PAVFs) are rare and mostly observed in children. However, the overall angioarchitecture, clinical features, treatments and long-term prognosis for pediatric patients remain unclear.
Clinical data of consecutive 42 pediatric PAVFs were documented and analysed. According to the differences of age distribution and clinical features, they were split into a younger group (≤3 years old; 20 cases) and an older group (3–14 years old; 22 cases).
Their mean age was 4.9±3.9 years, and the mean preoperative modified Rankin Scale (mRS) score was 1.64±1.57. Fourteen patients (33.3%) were asymptomatic, followed by epilepsy (21.4%), intracranial haemorrhage (16.7%), hydrocephalus (9.5%), developmental delay (7.1%), intermittent headache (7.1%) and congestive heart failure (4.8%). Annual bleeding rate and rebleeding rate before treatment reached 3.86% and 3.17%. Poor venous drainage including sinus dynamic obstruction (21 cases, 50.0%) and sinus occlusion (17 cases, 40.48%) were found with high frequency among these patients. Finally, 33 cases were cured (78.57%), and 4 cases faced surgery-related complications (9.52%). During 24–140 months’ follow-up, the mean mRS score reduced to 0.57±0.40. However, only 22 cases (52.38%) recovered to absolutely normal, and poor venous drainage was the risk factor for patients’ incomplete recovery (p=0.028, Exp(B)=14.692, 95% CI 1.346 to 160.392). Compared with the older group, younger group showed more chronic symptoms, more secondary pathological changes, more times treatment and worse prognosis (p=0.013, 0.002, 0.000 and 0.032, respectively).
Pediatric PAVF has different angioarchitectures, clinical features and prognoses in different age groups. Poor venous drainage is an important factor leading to poor prognosis, and it accounts for incomplete recovery in nearly half of patients.
Myocardial injury related to acute ischaemic stroke is common even without primary cardiac disease. We intended to determine associations between values of left ventricular ejection fraction (LVEF) and ischaemic stroke lesion sites.
Of a local database, patients with acute first-ever ischaemic stroke confirmed by brain imaging but without pre-existing heart disease were included. The cardiac morphology and LVEF were obtained from transthoracic or transesophageal echocardiography, and impaired LVEF was categorised as mild (35%–50%), moderate (34%–25%) and severe (<25%). Patient age, stroke severity, ischaemic lesion volume, prevalence of troponin I increase (>0.1 ng/mL), atrial fibrillation and cardiac wall motion abnormalities were assessed and compared between patients with and without impaired LVEF after stroke (significance: p<0.05). A multivariate voxelwise lesion analysis correlated LVEF after stroke with sites of ischaemic lesions.
Of 1209 patients who had a stroke, 231 (mean age 66.3±14.0 years) met the inclusion criteria; 40 patients (17.3%) had an impaired LVEF after stroke. Patients with impaired LVEF had higher infarct volumes (53.8 mL vs 30.0 mL, p=0.042), a higher prevalence of troponin increase (17.5% vs 4.2%, p=0.006), cardiac wall motion abnormalities (42.5% vs 5.2%, p<0.001) and atrial fibrillation (60.0% vs 26.2%, p<0.001) than patients with LVEF of >50%. The multivariate voxelwise lesion analysis yielded associations between decreased LVEF and damaged voxels in the insula, amygdala and operculum of the right hemisphere.
Our imaging analysis unveils a prominent role of the right hemispheric central autonomic network, especially of the insular cortex, in the brain–heart axis. Our results support preliminary evidence that acute ischaemic stroke in distinct brain regions of the central autonomic network may directly impair cardiac function and thus further supports the concept of a distinct stroke-heart syndrome.
This study aimed to assess whether pregnancy and puerperium were associated with the risk of brain arteriovenous malformation (bAVM) haemorrhage.
A retrospective review was conducted in Xiangya Hospital, Central South University from January 2012 to December 2021. A case–crossover design was adopted to calculate the incidence density of bAVM-related haemorrhage among female patients in risk (pregnancy and puerperium) and control (non-pregnancy and non-puerperium) periods, according to four scenarios observed in different populations (scenario I: patients with haemorrhagic bAVM of all ages; scenario II: patients with haemorrhagic bAVM of all ages, with at least one previous pregnancy; scenario III: patients with haemorrhagic bAVM who are of reproductive age (15–45 years); scenario IV: patients with haemorrhagic bAVM of reproductive age (15–45 years), with at least one previous pregnancy. Next, a comprehensive literature aggregation (up to April 2022) was performed for evidence synthesis.
Among the 311 female patients with haemorrhagic bAVM, a significant haemorrhage risk during pregnancy and puerperium was found in Scenarios I (relative risk [RR], 2.08; 95% CI, 1.28 to 3.39), II (RR, 3.21; 95% CI, 1.95 to 5.31) and IV (RR, 2.92; 95% CI, 1.73 to 4.93); however, a suggestive risk was found in scenario III (RR, 1.62; 95% CI, 0.99 to 2.67). Evidence synthesis revealed a consistent haemorrhage risk among patients of all ages (RR, 3.15; 95% CI, 1.93 to 5.15) and those of reproductive age (RR, 1.29; 95% CI, 0.89 to 1.86).
Compared with most previous studies, a higher but relatively moderate risk for bAVM-related haemorrhage was identified during pregnancy and puerperium. Individualised prevention and treatment strategies should be preferred when neurosurgeons make clinical decisions.
An analysis of the ASTER 2 trial revealed similar final recanalisation levels and clinical outcomes in acute large vessel occlusion (LVO) stroke between stent retrieval (SR) alone as a first-line mechanical thrombectomy (MT) technique (SR alone first-line) and concomitant use of contact aspiration (CA) plus SR as a first-line MT technique (SR+CA first-line). The purpose of the present study was to compare the safety and efficacy of SR+CA first-line with those of SR alone first-line for patients with LVO in China.
We conducted the present study by using the data from the ANGEL-ACT registry. We divided the selected patients into SR+CA first-line and SR alone first-line groups. We performed logistic regression and generalised linear models with adjustments to compare the angiographic and clinical outcomes, including successful/complete recanalisation after the first technique alone and all procedures, first-pass successful/complete recanalisation, number of passes, 90-day modified Rankin Scale, procedure duration, rescue treatment and intracranial haemorrhage within 24 hours.
Of the 1233 enrolled patients, 1069 (86.7%) received SR alone first-line, and 164 (13.3%) received SR+CA first-line. SR+CA first-line was associated with more thrombectomy passes (3 (2–4) vs 2 (1–2); β=1.77, 95% CI=1.55 to 1.99, p<0.001), and longer procedure duration (86 (60–129) min vs 80 (50–122) min; β=10.76, 95% CI=1.08 to 20.43, p=0.029) than SR alone first-line group. Other outcomes were comparable (all p>0.05) between the two groups.
Patients undergoing SR+CA first-line had more thrombectomy passes and longer procedure duration than patients undergoing SR alone first-line. Additionally, we suggested that SR+CA first-line was not superior to SR alone first-line in final recanalisation level, first-pass recanalisation level and 90-day clinical outcomes in the Chinese population.
Light transmission aggregometry (LTA) and CYP2C19 genotype analysis are commonly used to evaluate the antiplatelet effects of clopidogrel during the interventional treatment of intracranial aneurysms. The aim of this study was to determine which test can predict ischaemic events during these treatments.
Patient demographic information, imaging data, laboratory data and ischaemic complications were recorded. LTA and CYP2C19 genotype results were compared, and multiple linear regression was performed to examine factors related to platelet reactivity. Multivariate regression analysis was performed to determine whether LTA and CYP2C19 could predict ischaemic complications and to identify other clinical risk factors. Receiver operating characteristic curve analysis was conducted to calculate the cut-off value for predicting ischaemic complications. A subgroup analysis was also performed for different CYP2C19 genotype metabolisers, as well as for patients with flow diverters and traditional stents.
A total of 379 patients were included, of which 22 developed ischaemic events. Maximum platelet aggregation induced by ADP (ADP-MPA) could predict ischaemic events (p<0.001; area under the curve, 0.752 (95% CI 0.663 to 0.842)), and its cut-off value was 41.5%. ADP-MPA (p=0.001) and hypertension duration >10 years (p=0.022) were independent risk factors for ischaemic events, while the CYP2C19 genotype was not associated with ischaemic events. In the subgroup analysis, ADP-MPA could predict ischaemic events in fast metabolisers (p=0.004) and intermediate metabolisers (p=0.003). The cut-off value for ischaemic events was lower in patients with flow diverters (ADP-MPA=36.4%) than in patients with traditional stents (ADP-MPA=42.9%).
ADP-MPA can predict ischaemic complications during endovascular treatment of intracranial aneurysms. Patients with flow diverters require stronger antiplatelet medication than patients with traditional stents.