Association between perivascular spaces burden and future stroke risk in ischemic stroke and transient ischemic attack: A systematic review and meta-analysis.

INTRODUCTION: This meta-analysis aimed to explore the association of perivascular spaces (PVS) burden with the risks of future stroke events and mortality in patients with ischemic stroke and transient ischemic attack (TIA). METHODS: We systematically searched PubMed, Embase and Cochrane database from inception to 31 December 2023. We included eligible studies that reported adjusted estimated effects for future intracranial hemorrhage (ICH), ischemic stroke and mortality with baseline PVS burden in patients with ischemic stroke and TIA. Data were pooled using an inverse-variance method for fixed effect (FE) model and a restricted maximum likelihood (REML) method for random effects (RE) model. RESULTS: Thirteen observational studies (5 prospective, 8 retrospective) were included, comprising 20256 patients. Compared to 0 - 10 PVS at basal ganglia (BG), a higher burden (>10) of BG-PVS was significantly associated with an increased risk of future intracranial hemorrhage (adjusted hazards ratio [aHR] 2.79, 95% confidence interval [CI] 1.16 - 6.73, RE model; aHR 2.14, 95%CI 1.34 - 3.41, FE model; I2 = 64%, n = 17084 from four studies) followed-up for at least one year. There was no significant association between >10 BG-PVS and intracranial hemorrhage within 7 days after reperfusion therapy (adjusted odds ratio [aOR] 1.69, 95%CI 0.74 - 3.88, RE model; aOR 1.43, 95%CI 0.89 - 2.88, FE model; I2 = 67%, n = 1176 from four studies). We did not detect a significant association of recurrent ischemic stroke, mortality or disability with BG-PVS burden. Neither >10 PVS at centrum semiovale (CSO-PVS) nor increasing CSO-PVS burden was significantly associated with the risk of future intracerebral hemorrhage or ischemic stroke recurrence. CONCLUSIONS: Current evidence suggests that a higher BG-PVS burden may be associated with an increased risk of future intracranial hemorrhage in patients with ischemic stroke and TIA. PROSPERO registration number: CRD42021232713 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021232713.

White Matter Hyperintensities on Post-Stroke Balance and Gait Recovery: A Prospective Cohort Study Protocol.

INTRODUCTION: White matter hyperintensities (WMH) are commonly associated with balance and gait disturbances. Little is known whether WMH may affect post-stroke balance and gait recovery. We aim to investigate the association of post-stroke balance and gait recovery with imaging marker of WMH on magnetic resonance imaging (MRI). METHODS: This prospective cohort study will enroll consecutive patients with first-ever ischemic hemisphere stroke, between September 2023 and December 2024. Clinical data will be collected on day 30±3 and at 3-month after stroke onset. WMH on FLAIR are graded according to the modified Fazekas scale. Resting-state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) will be acquired to evaluate functional and structural connectivity. The primary endpoint is balance recovery, defined as a Postural Assessment Scale for Stroke score of 32 or higher at 3-month. The secondary endpoint is gait recovery, assessed using the modified Fugl-Meyer Gait Assessment at 3-month. We will investigate the association of post-stroke balance and gait recovery with WMH severity as well as WMH-related functional and structural connectivity. CONCLUSION: The study may contribute to clarify the effect of WMH on post-stroke balance and gait disorder recovery.

The Effect of Cerebellar Repetitive Transcranial Magnetic Stimulation on Dysphagia due to Posterior Circulation Stroke, a Randomized Controlled Trial Protocol.

INTRODUCTION: Cerebellum might be active during the task of swallowing. Little is known whether cerebellar repetitive transcranial magnetic stimulation (rTMS) could improve post-stroke dysphagia (PSD) due to occlusion in the posterior circulation. This paper describes the rationale and design of a randomized controlled trial that aims to determine the effect of cerebellar rTMS on dysphagia due to posterior circulation stroke. METHODS AND ANALYSIS: Thirty patients with PSD due to occlusion in the posterior circulation will be randomly divided to receive real (n = 20) or sham (n = 10) cerebellar rTMS. Patients in the real rTMS group will receive 250 pulses rTMS at a low intensity with 10 Hz frequency for 10 days (five consecutive days per week). The severity of dysphagia will be assessed with videofluoroscopic swallowing study (VFSS) using the Rosenbek penetration aspiration scale (PAS), the pharyngeal constriction ratio (PCR), and the dysphagia outcome and severity scale (DOSS) before and immediately after the last session and then again after 1 and 3 months. The functional magnetic resonance imaging (fMRI) will be assessed before and after the last session and then again after 1 month and 3 months. The primary outcome is the improvement of swallowing function determined by PAS, PCR, and DOSS. The secondary outcomes include changes in brain connectivity network detected using fMRI. DISCUSSION: This study will determine whether cerebellar rTMS improves dysphagia due to posterior circulation stroke in Chinese patients. Our findings will contribute to a new approach for swallowing function recovery after posterior circulation stroke.

Should patients with epilepsy be vaccinated against coronavirus disease 2019? A systematic review and meta-analysis.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) vaccination coverage, willingness, and safety profiles in patients with epilepsy remain poorly understood. We aimed to summarize the available evidence of COVID-19 vaccination coverage, willingness, and safety profiles among patients with epilepsy. METHODS: We performed a literature search in the Pubmed, EMBASE, and Cochrane Central Register database between 1 January 2020 and 30 April 2022. We included eligible studies that provided information on the COVID-19 vaccination coverage, willingness, and safety profiles among patients with epilepsy. We investigated the association between baseline characteristics of patients with epilepsy and unvaccination status using a fixed-effect model. We calculated the pooled overall willingness to be vaccinated against COVID-19. We systematically reviewed the safety profiles after COVID-19 vaccination in patients with epilepsy. RESULTS: Ten eligible observational studies and two case reports yielded 2589 participants with epilepsy or their caregivers. Among 2145 participants that provided the information of vaccination status, 1508 (70.3%) patients with epilepsy were not administered COVID-19 vaccine, and 58% (95%CI 40-75%) of respondents were willing to be vaccinated against COVID-19. Seizure status (active versus inactive, OR 1.84 95%CI 1.41-2.39, I2 = 0%) rather than seizure type (focal versus non-focal, OR 1.22 95%CI 0.94-1.58, I2 = 0%) was associated with COVID-19 unvaccination status. Vaccines were well-tolerated; epilepsy-related problems such as increase in seizure frequency and status epilepticus after COVID-19 vaccination were uncommon. CONCLUSIONS: Our findings suggest a low COVID-19 vaccination coverage and willingness in patients with epilepsy. Vaccination against COVID-19 appears to be well-tolerated and safe in patients with epilepsy, supporting a positive outlook toward vaccination in this population.

Determinants for a low dose of alteplase and its relationship to a lower intracerebral bleeding risk in acute ischemic stroke.

Background: Factors for the utilization of intravenous thrombolysis with a low-dose of alteplase (0.6mg/kg) and whether the low-dose of alteplase could reduce the risk of intracerebral bleeding in acute ischemic stroke (AIS) remains uncertain. Aims: We aimed to investigate determinants for the utilization of intravenous thrombolysis with a low-dose of alteplase. We further assessed the association between the low-dose of alteplase and the intracerebral bleeding risk in AIS patients. Method: We included AIS patients who received intravenous thrombolysis using alteplase in this multicenter retrospective observational study. We investigated the association between baseline characteristics and the utilization of a low-dose of alteplase to identify determinants. We assessed the association of the low-dose of alteplase with the risk of symptomatic intracranial hemorrhage (sICH) using a multivariable logistic regression model. We further compared the rate of sICH and any ICH in patients in the low-dose group to those in the standard-dose group, using propensity score-matching data. Results: A total of 506 AIS patients were included in this study. The mean age was 67 (interquartile range [IQR] 59-75), and 178 (35.2%) were women. A total of 96 patients were treated with the low-dose. Age (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 1.00 -1.04, p = 0.042), having a previous ischemic stroke (adjusted OR 2.01, 95%CI 1.11 - 3.64 p = 0.021) and increasing baseline systolic blood pressure (adjusted OR 1.12, 95%CI 1.00 - 1.26, p = 0.049) were determinants for the utilization of the low-dose. Multivariable logistic regression analysis showed that the low-dose was significantly associated with a reduced risk of sICH (adjusted OR 0.13, 95%CI 0.03 - 0.62, p = 0.01). Propensity score analysis showed that the rate of sICH was significantly lower in the low-dose group compared to standard-dose group (2 [2.3%] vs 10 [11.4%], p = 0.032). There was no significant difference in the rate of any ICH between two groups (14 [15.9%] vs 18 [20.5%], p = 0.434). Conclusions: Patients with increasing age, a higher baseline systolic blood pressure, and previous ischemic stroke were at a higher odd of receiving a low-dose of alteplase. The low-dose was associated with a lower risk of developing symptomatic intracranial hemorrhage.

Intravenous thrombolysis prior to endovascular treatment for acute ischemic stroke: a meta-analysis.

OBJECTIVES: Whether intravenous thrombolysis provides additional benefits before direct endovascular treatment (dEVT) in acute ischemic stroke remains unclear. We aimed to compare the functional and safety outcomes of dEVT to endovascular treatment with bridging using intravenous thrombolysis (BT) in acute ischemic stroke. METHODS: This meta-analysis included currently available eligible randomized clinical trials (RCTs) by searching in the PubMed, EMBASE, Cochrane Central Register, and the International Stroke Conference and European Stroke Organisation Conference posted abstracts. RESULTS: The six included RCTs yielded 2334 participants (mean age, 69.8 years [SD, 11.4]; women, 44.3%; 1164 in dEVT group and 1170 in BT group). We found not significantly different 90-day functional outcomes of modified Rankin scale (mRS 0 - 2, odds ratio [OR] 0.93, 95%CI 0.79 - 1.09; mRS 0 - 1, OR 0.99, 95%CI 0.82 - 1.18), mortality (OR 1.08, 95%CI 0.86 - 1.35), and symptomatic intracranial hemorrhage (OR 0.72, 95%CI 0.49 - 1.07) for patients in dEVT and BT group. Patients treated with dEVT were less likely to experience successful recanalization (OR 0.72, 95%CI 0.57 - 0.92, p = 0.009) and any intracranial hemorrhage (OR 0.81, 95%CI 0.68 - 0.97, p = 0.02). There were no significant differences regarding procedural complications between the two groups. CONCLUSION: This meta-analysis showed no significant differences in 90-day functional outcomes or mortality between dEVT and BT, but a lower possibility of successful recanalization and intracranial hemorrhage for dEVT.

Small Vessel Disease and Ischemic Stroke Risk During Anticoagulation for Atrial Fibrillation After Cerebral Ischemia.

BACKGROUND AND PURPOSE: The causes of recurrent ischemic stroke despite anticoagulation for atrial fibrillation are uncertain but might include small vessel occlusion. We investigated whether magnetic resonance imaging markers of cerebral small vessel disease (SVD) are associated with ischemic stroke risk during follow-up in patients anticoagulated for atrial fibrillation after recent ischemic stroke or transient ischemic attack. METHODS: We analyzed data from a prospective multicenter inception cohort study of ischemic stroke or transient ischemic attack anticoagulated for atrial fibrillation (CROMIS-2 [Clinical Relevance of Microbleeds in Stroke Study]). We rated markers of SVD on baseline brain magnetic resonance imaging: basal ganglia perivascular spaces (number ≥11); cerebral microbleeds (number ≥1); lacunes (number ≥1); and white matter hyperintensities (periventricular Fazekas grade 3 or deep white matter Fazekas grade ≥2). We investigated the associations of SVD presence (defined as presence of ≥1 SVD marker) and severity (composite SVD score) with the risk of ischemic stroke during follow-up using a Cox proportional hazards model adjusted for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65-74, female score. RESULTS: We included 1419 patients (mean age: 75.8 years [SD, 10.4]; 42.1% female). The ischemic stroke rate during follow-up in patients with any SVD was 2.20 per 100-patient years (95% CI, 1.60-3.02), compared with 0.98 per 100 patient-years (95% CI, 0.59-1.62) in those without SVD (P=0.008). After adjusting for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65-74, female score, SVD presence remained significantly associated with ischemic stroke during follow-up (hazard ratio, 1.89 [95% CI, 1.01-3.53]; P=0.046); the risk of recurrent ischemic stroke increased with SVD score (hazard ratio per point increase, 1.33 [95% CI, 1.04-1.70]; P=0.023). CONCLUSIONS: In patients anticoagulated for atrial fibrillation after ischemic stroke or transient ischemic attack, magnetic resonance imaging markers of SVD are associated with an increased risk of ischemic stroke during follow-up; improved stroke prevention treatments are required in this population. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02513316.

Bone marrow-derived mesenchymal stem cells improve post-ischemia neurological function in rats via the PI3K/AKT/GSK-3ß/CRMP-2 pathway.

BACKGROUND: Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) is a potential therapy for cerebral ischemia. However, the underlying protective mechanism remains undetermined. Here, we tested the hypothesis that transplantation of BMSCs via intravenous injection can alleviate neurological functional deficits through activating PI3K/AKT signaling pathway after cerebral ischemia in rats. METHODS: A cerebral ischemic rat model was established by the 2 h middle cerebral artery occlusion (MCAO). Twenty-four hours later, BMSCs (1 × 106 in 1 ml PBS) from SD rats were injected into the tail vein. Neurological function was evaluated by modified neurological severity score (mNSS) and modified adhesive removal test before and on d1, d3, d7, d10 and d14 after MCAO. Protein expressions of AKT, GSK-3ß, CRMP-2 and GAP-43 were detected by Western-bolt. NF-200 was detected by immunofluorescence. RESULTS: BMSCs transplantation did not only significantly improve the mNSS score and the adhesive-removal somatosensory test after MCAO, but also increase the density of NF-200 and the expression of p-AKT, pGSK-3ß and GAP-43, while decrease the expression of pCRMP-2. Meanwhile, these effects can be suppressed by LY294002, a specific inhibitor of PI3K/AKT. CONCLUSION: These data suggest that transplantation of BMSCs could promote axon growth and neurological deficit recovery after MCAO, which was associated with activation of PI3K/AKT /GSK-3ß/CRMP-2 signaling pathway.

Prevalence and outcomes of re-positive nucleic acid tests in discharged COVID-19 patients.

The prevalence and outcomes of patients who had re-activation of coronavirus disease 2019 (COVID-19) after discharge remain poorly understood. We included 126 consecutively confirmed cases of COVID-19 with 2-month follow-up data after discharge in this retrospective study. The upper respiratory specimen using a reverse-transcription polymerase chain reaction test of three patients (71 years [60-76]) were positive within 11-20 days after their discharge, with an event rate of 19.8 (95%CI 2.60-42.1) per 1,000,000 patient-days. Moreover, all re-positive patients were asymptomatic. Our findings suggest that few recovered patients may still be virus carriers even after reaching the discharge criteria.

Six-month follow-up of functional status in discharged patients with coronavirus disease 2019.

BACKGROUND: The long-term functional outcome of discharged patients with coronavirus disease 2019 (COVID-19) remains unresolved. We aimed to describe a 6-month follow-up of functional status of COVID-19 survivors. METHODS: We reviewed the data of COVID-19 patients who had been consecutively admitted to the Tumor Center of Union Hospital (Wuhan, China) between 15 February and 14 March 2020. We quantified a 6-month functional outcome reflecting symptoms and disability in COVID-19 survivors using a post-COVID-19 functional status scale ranging from 0 to 4 (PCFS). We examined the risk factors for the incomplete functional status defined as a PCFS > 0 at a 6-month follow-up after discharge. RESULTS: We included a total of 95 COVID-19 survivors with a median age of 62 (IQR 53-69) who had a complete functional status (PCFS grade 0) at baseline in this retrospective observational study. At 6-month follow-up, 67 (70.5%) patients had a complete functional outcome (grade 0), 9 (9.5%) had a negligible limited function (grade 1), 12 (12.6%) had a mild limited function (grade 2), 7 (7.4%) had moderate limited function (grade 3). Univariable logistic regression analysis showed a significant association between the onset symptoms of muscle or joint pain and an increased risk of incomplete function (unadjusted OR 4.06, 95% CI 1.33-12.37). This association remained after adjustment for age and admission delay (adjusted OR 3.39, 95% CI 1.06-10.81, p = 0.039). CONCLUSIONS: A small proportion of discharged COVID-19 patients may have an incomplete functional outcome at a 6-month follow-up; intervention strategies are required.

The effect of vascular risk factor burden on the severity of COVID-19 illness, a retrospective cohort study.

BACKGROUND: Patients with cardiovascular comorbidities are at high risk of poor outcome from COVID-19. However, how the burden (number) of vascular risk factors influences the risk of severe COVID-19 disease remains unresolved. Our aim was to investigate the association of severe COVID-19 illness with vascular risk factor burden. METHODS: We included 164 (61.8 ± 13.6 years) patients with COVID-19 in this retrospective study. We compared the difference in clinical characteristics, laboratory findings and chest computed tomography (CT) findings between patients with severe and non-severe COVID-19 illness. We evaluated the association between the number of vascular risk factors and the development of severe COVID-19 disease, using a Cox regression model. RESULTS: Sixteen (9.8%) patients had no vascular risk factors; 38 (23.2%) had 1; 58 (35.4%) had 2; 34 (20.7%) had 3; and 18 (10.9%) had ≥4 risk factors. Twenty-nine patients (17.7%) experienced severe COVID-19 disease with a median (14 [7-27] days) duration between onset to developing severe COVID-19 disease, an event rate of 4.47 per 1000-patient days (95%CI 3.10-6.43). Kaplan-Meier curves showed a gradual increase in the risk of severe COVID-19 illness (log-rank P < 0.001) stratified by the number of vascular risk factors. After adjustment for age, sex, and comorbidities as potential confounders, vascular risk factor burden remained associated with an increasing risk of severe COVID-19 illness. CONCLUSIONS: Patients with increasing vascular risk factor burden have an increasing risk of severe COVID-19 disease, and this population might benefit from specific COVID-19 prevention (e.g., self-isolation) and early hospital treatment measures.

Treadmill exercise enhances therapeutic potency of transplanted bone mesenchymal stem cells in cerebral ischemic rats via anti-apoptotic effects.

BACKGROUND: The transplantation of bone marrow stromal cells (MSCs) has proved to ameliorate ischemic brain injury in animals, but most transplanted MSCs undergo apoptosis in the ischemic penumbra, greatly compromising the therapeutic value of this treatment. Meanwhile, cell apoptosis can be inhibited by post-ischemia exercise which has been demonstrated to improve the expression of related anti-apoptotic proteins. The present study investigated whether treadmill exercise enhances the neuroprotective effects of transplanted MSCs in a rat experimental stroke model. RESULT: Rats were subjected to 2-h middle cerebral artery occlusion (MCAO). Twenty-four hours after reperfusion, they were assigned randomly to receive no MSCs treatment and no exercise (control group), intravenous transplantation of MSCs and treadmill exercise (MSCs + Ex group), MSCs transplantation only (MSCs group) and treadmill exercise only (Ex group). Neurological assessment, TUNEL staining and western blot were performed. Compared with the MSCs group and Ex group, the MSCs + Ex group reported markedly improved neurological function, significantly decreased apoptotic cells, and increased expressions of survivin and bcl-2 (p < 0.05 or p < 0.01, respectively). Interestingly, the treadmill exercise significantly inhibited the apoptosis of transplanted MSCs. As a result, the number of engrafted MSCs in the MSCs + Ex group was significantly higher than that in the MSC group (p < 0.01). CONCLUSIONS: Treadmill exercise enhances the therapeutic potency of MSCs by improving neurological function and possibly inhibiting the apoptosis of neuron cells and transplanted MSCs. These effects may involve an increased expression of survivin and bcl-2.

Association between atrial cardiopathy and stroke severity in acute ischemic stroke.

In this hospital-based cross-sectional analytic study, we retrospectively reviewed clinical data of patients with acute ischemic stroke (AIS) between January 2017 and April 2023. Atrial cardiopathy was defined as any presence of the following: left atrial diameter ≥ 52 mm (males) or ≥ 47 mm (females), elevated P-wave terminal force in V1 > 5000 µV ms, or serum N terminal pro B type natriuretic peptide > 250 pg/ml. Initial stroke severity was defined by the National Institutes of Health Stroke Scale (NIHSS; moderate-to-severe, ≥ 5; and severe, ≥ 15). Univariate and multivariate binary logistic regression analyses were performed to assess the association between atrial cardiopathy and stroke severity. Among 662 AIS patients (mean age 70 years [interquartile range 61-78], 31.3% women), 303 (45.8%) had atrial cardiopathy. Multivariable logistic regression analysis showed that the presence of atrial cardiopathy was significantly associated with a higher odd of moderate-to-severe stroke (adjusted odds ratio [OR] 2.16, 95% confidence interval [CI] 1.46-3.20, p < 0.001) and severe stroke (adjusted OR 4.89, 95%CI 2.45-9.76, p < 0.001). This association remained significant in a sensitivity analysis excluding those with atrial fibrillation or coronary artery disease. Findings of the current study revealed that the association of atrial cardiopathy was with initial stroke severity independent of atrial fibrillation and was even confirmed in patients without atrial fibrillation; future studies to explore improved stroke prevention strategies for patients with atrial cardiopathy are needed.

Sex difference in the association between triglyceride and intracerebral bleeding risk after intravenous thrombolysis for acute ischemic stroke, a multi-center retrospective study.

Background: Whether the relationship of intracerebral bleeding risk with lipid profile may vary by sex remains unclear. This study aims to investigate potential sex differences in the association between lipid profile and the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) who received intravenous thrombolysis using recombinant tissue plasminogen activator (r-tPA). Methods: This multicenter retrospective observational study analyzed patients with AIS treated with intravenous r-tPA. sICH was defined as a worsening of 4 or higher points in the National Institutes of Health Stroke Scale (NIHSS) score within 36 hours after intravenous thrombolysis in any hemorrhage subtype. We assessed the odds ratio (OR) with 95% confidence interval (CI) of lipid profile for sICH for each sex using logistic regression models adjusted for potential confounding factors. Results: Of 957 participants (median age 68 (interquartile range, 59-75), men 628 (65.6%)), 56 sICH events (36 (5.7%) in men and 20 (6.1%) in women) were observed. The risk of sICH in men decreased with increasing serum levels of triglyceride after adjustment for confounding factors (vs lowest tertile, medium tertile OR 0.39, 95% CI [0.17-0.91], top tertile OR 0.33, 95% CI [0.13-0.84], overall p = 0.021; per point increase, adjusted OR 0.29, 95% CI [0.13-0.63], p = 0.002). Neither serum levels of total cholesterol nor low-density lipoprotein (LDL) was associated with sICH in men. In women, there was no association between any of the lipid levels and the risk of sICH. Conclusions: This study indicated that the association between serum levels of triglyceride and sICH may vary by sex. In men, increased triglyceride levels decrease the risk of sICH; in women, this association was lost. Further studies on the biological mechanisms for sex differences in stroke risk associated with triglyceride are needed.

Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds.

BACKGROUND AND OBJECTIVES: The association between statin use and the risk of intracranial hemorrhage (ICrH) following ischemic stroke (IS) or transient ischemic attack (TIA) in patients with cerebral microbleeds (CMBs) remains uncertain. This study investigated the risk of recurrent IS and ICrH in patients receiving statins based on the presence of CMBs. METHODS: We conducted a pooled analysis of individual patient data from the Microbleeds International Collaborative Network, comprising 32 hospital-based prospective studies fulfilling the following criteria: adult patients with IS or TIA, availability of appropriate baseline MRI for CMB quantification and distribution, registration of statin use after the index stroke, and collection of stroke event data during a follow-up period of ≥3 months. The primary endpoint was the occurrence of recurrent symptomatic stroke (IS or ICrH), while secondary endpoints included IS alone or ICrH alone. We calculated incidence rates and performed Cox regression analyses adjusting for age, sex, hypertension, atrial fibrillation, previous stroke, and use of antiplatelet or anticoagulant drugs to explore the association between statin use and stroke events during follow-up in patients with CMBs. RESULTS: In total, 16,373 patients were included (mean age 70.5 ± 12.8 years; 42.5% female). Among them, 10,812 received statins at discharge, and 4,668 had 1 or more CMBs. The median follow-up duration was 1.34 years (interquartile range: 0.32-2.44). In patients with CMBs, statin users were compared with nonusers. Compared with nonusers, statin therapy was associated with a reduced risk of any stroke (incidence rate [IR] 53 vs 79 per 1,000 patient-years, adjusted hazard ratio [aHR] 0.68 [95% CI 0.56-0.84]), a reduced risk of IS (IR 39 vs 65 per 1,000 patient-years, aHR 0.65 [95% CI 0.51-0.82]), and no association with the risk of ICrH (IR 11 vs 16 per 1,000 patient-years, aHR 0.73 [95% CI 0.46-1.15]). The results in aHR remained consistent when considering anatomical distribution and high burden (≥5) of CMBs. DISCUSSION: These observational data suggest that secondary stroke prevention with statins in patients with IS or TIA and CMBs is associated with a lower risk of any stroke or IS without an increased risk of ICrH. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with IS or TIA and CMBs, statins lower the risk of any stroke or IS without increasing the risk of ICrH.

Clinical Associations and Prognostic Value of MRI-Visible Perivascular Spaces in Patients With Ischemic Stroke or TIA: A Pooled Analysis

BACKGROUND AND OBJECTIVES: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. METHODS: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. RESULTS: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; p = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. DISCUSSION: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH.

A comparison of low- versus standard-dose bridging alteplase in acute ischemic stroke mechanical thrombectomy using indirect methods.

Background: Whether low-dose alteplase is similar to standard-dose bridging alteplase prior to endovascular mechanical thrombectomy in patients with acute ischemic stroke (AIS) remains uncertain. Aims: The aim of this study was to compare the efficacy and safety outcomes of low- versus standard-dose bridging alteplase therapy (BT) in patients with acute ischemic stroke (AIS) who are eligible for intravenous thrombolysis (IVT) within 4.5 h after onset. Methods: We conducted an indirect comparison of low- versus standard-dose bridging alteplase before mechanical thrombectomy in AIS of current available clinical randomized controlled trials (RCTs) that compared direct mechanical thrombectomy treatment (dMT) to BT. Primary efficacy outcomes were functional independence and excellent recovery defined as a dichotomized modified Rankin Scale (mRS) 0-2 and 0-1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and any intracranial hemorrhage (ICH). Results: We included six RCTs of 2334 AIS patients in this analysis, including one trial using low-dose bridging alteplase (n = 103) and five trials using standard-dose bridging alteplase (n = 1067) against a common comparator (dMT). Indirect comparisons of low- to standard-dose bridging alteplase yielded an odds ratio (OR) of 0.84 (95% CI 0.47-1.50) for 90-day mRS 0-2, 1.18 (95% CI 0.65-2.12) for 90-day mRS 0-1, 1.21 (95% CI 0.44-3.36) for mortality, and 1.11 (95% CI 0.39-3.14) for successful recanalization. There were no significant differences in the odds for sICH (OR 1.05, 95% CI 0.32-3.41) or any ICH (OR 1.71, 95% CI 0.94-3.10) between low- and standard-dose bridging alteplase. Conclusion: Indirect evidence shows that the effects of low- and standard-dose bridging alteplase are similar for key efficacy and safety outcomes. Due to the wide confidence intervals, larger randomized trials comparing low- and standard-dose alteplase bridging therapy are required.

Association between Triglyceride-Glucose Index and Early Neurological Outcomes after Thrombolysis in Patients with Acute Ischemic Stroke.

BACKGROUND: The triglyceride-glucose (TyG) index is a novel biomarker of insulin resistance which might plausibly influence endogenous fibrinolysis and thus early neurological outcomes in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis using recombinant tissue-plasminogen activator. METHODS: We included consecutive AIS patients within 4.5 h of symptom onset undergoing intravenous thrombolysis between January 2015 and June 2022 in this multi-center retrospective observational study. Our primary outcome was early neurological deterioration (END), defined as ≥2 (END2) or ≥ 4 (END4) National Institutes of Health Stroke Scale (NIHSS) score worsening compared to the initial NIHSS score within 24 h of intravenous thrombolysis. Our secondary outcome was early neurological improvement (ENI), defined as a lower NIHSS score at discharge. TyG index was calculated using the log scale of fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2. We evaluated the association of END and ENI with TyG index using a logistic regression model. RESULTS: A total of 676 patients with AIS were evaluated. The median age was 68 (Interquartile range, IQR (60-76) years old), and 432 (63.9%) were males. A total of 89 (13.2%) patients developed END2, 61 (9.0%) patients developed END4, and 492 (72.7%) experienced ENI. In multivariable logistic regression analysis, after adjustment for confounding factors, TyG index was significantly associated with increased risks of END2 (categorical variable, vs. lowest tertile, medium tertile odds ratio [OR] 1.05, 95% confidence interval, CI 0.54-2.02, highest tertile OR 2.94, 95%CI 1.64-5.27, overall p < 0.001) and END4 (categorical variable, vs. lowest tertile, medium tertile OR 1.21, 95%CI 0.54-2.74, highest tertile OR 3.80, 95%CI 1.85-7.79, overall p < 0.001), and a lower probability of ENI (categorical variable, vs. lowest tertile, medium tertile OR 1.00, 95%CI 0.63-1.58, highest tertile OR 0.59, 95%CI 0.38-0.93, overall p = 0.022). CONCLUSIONS: Increasing TyG index was associated with a higher risk of END and a lower probability of ENI in patients with acute ischemic stroke treated with intravenous thrombolysis.

Future COVID-19 Booster Vaccine Refusal in Healthcare Workers after a Massive Breakthrough Infection Wave, a Nationwide Survey-Based Study.

Background: An unprecedented coronavirus disease 2019 (COVID-19) wave occurred in China between December 2022 and January 2023, challenging the efficacy of the primary series of COVID-19 vaccines. The attitudes toward future COVID-19 booster vaccines (CBV) after the massive breakthrough infection among healthcare workers remain unknown. This study aimed to explore the prevalence and determinants of future CBV refusal after the unprecedented COVID-19 wave among healthcare workers. Methods: Between 9 and 19 February 2023, a cross-sectional nationwide online survey was conducted using a self-administered questionnaire vaccine among healthcare workers in China. Sociodemographics, profession, presence of chronic medical conditions, previous COVID-19 infection, attitudes towards future CBV, and reasons for future CBV refusal were collected. We estimated odds ratio [OR] with 95% confidence interval [CI] using a multivariable logistic regression model to explore the factors associated with future CBV refusal. Results: Among the 1618 participants who completed the survey, 1511 respondents with two or more doses of COVID-19 vaccines were analyzed. A total of 648 (41.8%) of respondents were unwilling to receive a future CBV. Multivariable logistic regression analysis revealed the association of CBV refusal with profession (vs. other staff, physician-adjusted OR 1.17, 95%CI 0.79-1.72, nurse-adjusted OR 1.88, 95%CI 1.24-2.85, p = 0.008), history of allergy (adjusted OR 1.72, 95%CI 1.05-2.83, p = 0.032), a lower self-perceived risk of future COVID-19 infection (p < 0.001), and a lower belief in CBV effectiveness (p = 0.014), safety (p < 0.001), and necessities for healthcare workers and the public (p < 0.001, respectively). Conclusions: Our findings highlight that a considerable proportion of healthcare workers were against a future booster dose after an unprecedented COVID-19 wave. Self-perception of future COVID-19 risk, and potential harm or doubtful efficacy of vaccines are the main determinants. Our findings may help public health authorities to establish future COVID-19 vaccination programs.