Detecting prokaryote-specific gene and other bacterial signatures in thrombi from patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Microbial infection has been associated with thrombogenesis. This study aimed to detect bacterium-specific genes and other signatures in thrombi from patients with acute ischemic stroke and to relate these signatures to clinical characteristics. METHODS: Blood samples were collected before thrombectomy procedures, and thrombus samples were obtained during the procedure. Identification and classification of bacteria in the samples were accomplished using 16 S rRNA gene sequencing. Bacterium-specific structures were observed with transmission electron microscopy. Bacterium-specific biomarkers were detected through immunohistochemical staining. RESULTS: 16 S rRNA gene was detected in 32.1% of the thrombus samples from 81 patients. Bacillus (0.04% vs. 0.00046%, p = 0.003), Parabacteroides (0.20% vs. 0.09%, p = 0.029), Prevotella (1.57% vs. 0.38%, p = 0.010), Streptococcus (1.53% vs. 0.29%, p = 0.001), Romboutsia (0.18% vs. 0.0070%, p = 0.029), Corynebacterium (1.61% vs. 1.26%, p = 0.026) and Roseburia (0.53% vs. 0.05%, p = 0.005) exhibited significantly higher abundance in thrombi compared to arterial blood. Bacteria-like structures were observed in 22 (27.1%), while whole bacteria-like structures were observed in 7 (8.6%) thrombi under transmission electron microscopy. Immunohistochemical staining detected bacterium-specific monocyte/macrophage markers in 51 (63.0%) out of 81 thrombi. Logistic regression analysis indicated that alcohol consumption was associated with a higher bacteria burden in thrombi (odds ratio = 3.19; 95% CI, 1.10-9.27; p = 0.033). CONCLUSION: Bacterial signatures usually found in the oral cavity and digestive tract were detected in thrombi from patients with ischemic stroke. This suggests a potential involvement of bacterial infection in the development of thrombosis. Long-term alcohol consumption may potentially enhance this possibility.

A non-contrast computed tomography-based radiomics nomogram for the prediction of hematoma expansion in patients with deep ganglionic intracerebral hemorrhage.

Background and purpose: Hematoma expansion (HE) is a critical event following acute intracerebral hemorrhage (ICH). We aimed to construct a non-contrast computed tomography (NCCT) model combining clinical characteristics, radiological signs, and radiomics features to predict HE in patients with spontaneous ICH and to develop a nomogram to assess the risk of early HE. Materials and methods: We retrospectively reviewed 388 patients with ICH who underwent initial NCCT within 6 h after onset and follow-up CT within 24 h after initial NCCT, between January 2015 and December 2021. Using the LASSO algorithm or stepwise logistic regression analysis, five models (clinical model, radiological model, clinical-radiological model, radiomics model, and combined model) were developed to predict HE in the training cohort (n = 235) and independently verified in the test cohort (n = 153). The Akaike information criterion (AIC) and the likelihood ratio test (LRT) were used for comparing the goodness of fit of the five models, and the AUC was used to evaluate their ability in discriminating HE. A nomogram was developed based on the model with the best performance. Results: The combined model (AIC = 202.599, χ2 = 80.6) was the best fitting model with the lowest AIC and the highest LRT chi-square value compared to the clinical model (AIC = 232.263, χ2 = 46.940), radiological model (AIC = 227.932, χ2 = 51.270), clinical-radiological model (AIC = 212.711, χ2 = 55.490) or radiomics model (AIC = 217.647, χ2 = 57.550). In both cohorts, the nomogram derived from the combined model showed satisfactory discrimination and calibration for predicting HE (AUC = 0.900, sensitivity = 83.87%; AUC = 0.850, sensitivity = 80.10%, respectively). Conclusion: The NCCT-based model combining clinical characteristics, radiological signs, and radiomics features could efficiently discriminate early HE, and the nomogram derived from the combined model, as a non-invasive tool, exhibited satisfactory performance in stratifying HE risks.

Predictors of mortality for acute vertebrobasilar artery occlusion receiving endovascular treatment.

OBJECTIVES: Acute vertebrobasilar artery occlusion (VBAO) is a devastating type of stroke with a high mortality rate. This study aimed to investigate the predictors of 3-month and 1-year mortality in VBAO patients receiving endovascular treatment (EVT). MATERIALS & METHODS: Consecutive acute VBAO patients undergoing EVT between January 2014 and December 2019 were retrospectively analyzed in a prospectively maintained database. Multivariate logistical regression models were used to explore the potential predictors of mortality at 3 months and 1 year, respectively. The discrimination of the final model was assessed with the area under the receiver operating characteristic curve. RESULTS: A total of 100 patients were enrolled in this study (mean age 62 years; 77.0% male). After excluding patients lost to follow-up, the overall mortality rate was 34.3% (34/99) at 3 months and 45.4% (44/97) at 1 year. The Glasgow Coma Scale (GCS) score at 24 h (Odds ratio [OR], 0.676; 95% confidence interval [CI], 0.540-0.846; p = .001) and mechanical ventilation (MV) (OR, 7.356; 95% CI, 2.200-24.593; p = .001) were predictors of 3-month mortality after adjusting for potential confounders in multivariable analysis. Furthermore, the GCS score at 24 h (OR, 0.714; 95% CI, 0.590-0.864; p = .001), intracranial hemorrhage (OR, 7.330; 95% CI, 1.772-30.318; p = .006), and MV (OR, 5.804; 95% CI, 1.841-18.294; p = .003) were independently associated with mortality at 1 year. Sensitivity analyses showed similar results. CONCLUSION: The 24-h GCS score and MV were common predictors of 3-month and 1-year mortality, and ICH was an additional predictor of 1-year mortality.

A Pre-Interventional Scale to Predict in situ Atherosclerotic Thrombosis in Acute Vertebrobasilar Artery Occlusion Patients.

Background and Purpose: Determining the occlusion mechanism before endovascular treatment (EVT) is of great significance for acute large vessel occlusion patients. We aimed to develop and validate a simple pre-EVT scale with readily available variables for predicting in situ atherosclerotic thrombosis (ISAT) in acute vertebrobasilar artery occlusion (VBAO) patients. Materials and Methods: Consecutive patients were retrieved from Nanjing Stroke Registry Program between January 2014 and December 2019 as a derivation cohort. Anonymous data of consecutive patients between January 2014 and December 2019 were collected from another comprehensive stroke center as an external validation cohort. Demographics, medical histories, and clinical characteristics were collected. ISAT was defined according to the following criteria: (a) detection of moderate to severe (≥50%) stenosis or stenosis with significant distal flow impairment at the occluded segment when successful reperfusion was achieved; (b) transient visualization of eccentric plaque contour or a recurrent re-occlusion tendency when reperfusion was unsuccessful. Logistic regression was taken to develop a predictive scale. The performance of the scale was assessed by area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow test. Results: ISAT was observed in 41 of 95 (43.2%) patients included in the derivation cohort. The ISAT predictive scale consisted of three pre-interventional predictors, including the history of hypertension, atrial fibrillation rhythm, and baseline serum glucose level ≥7.55 mmol/L. The model depicted acceptable calibration (Hosmer-Lemeshow test, P = 0.554) and good discrimination (AUC, 0.853; 95% confidence interval, 0.775-0.930). The optimal cutoff value of the ISAT scale was 1 point with 95.1% sensitivity, 64.8% specificity, and 77.9% accuracy. In the validation cohort, the discrimination ability was still promising with an AUC value of 0.800 (0.682-0.918). Conclusion: The three-item scale comprised of the history of hypertension, atrial fibrillation rhythm, and dichotomous serum glucose level had a promising predictive value for ISAT before EVT in acute VBAO patients.

Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST): an open-label, randomised controlled trial.

BACKGROUND: Previous randomised trials have shown an overwhelming benefit of mechanical thrombectomy for treating patients with stroke caused by large vessel occlusion of the anterior circulation. Whether endovascular treatment is beneficial for vertebrobasilar artery occlusion remains unknown. In this study, we aimed to investigate the safety and efficacy of endovascular treatment of acute strokes due to vertebrobasilar artery occlusion. METHODS: We did a multicentre, randomised, open-label trial, with blinded outcome assessment of thrombectomy in patients presenting within 8 h of vertebrobasilar occlusion at 28 centres in China. Patients were randomly assigned (1:1) to endovascular therapy plus standard medical therapy (intervention group) or standard medical therapy alone (control group). The randomisation sequence was computer-generated and stratified by participating centres. Allocation concealment was implemented by use of sealed envelopes. The primary outcome was a modified Rankin scale (mRS) score of 3 or lower (indicating ability to walk unassisted) at 90 days, assessed on an intention-to-treat basis. The primary safety outcome was mortality at 90 days. Secondary safety endpoints included the rates of symptomatic intracranial haemorrhage, device-related complications, and other severe adverse events. The BEST trial is registered with ClinicalTrials.gov, NCT02441556. FINDINGS: Between April 27, 2015, and Sept 27, 2017, we assessed 288 patients for eligibility. The trial was terminated early after 131 patients had been randomly assigned (66 patients to the intervention group and 65 to the control group) because of high crossover rate and poor recruitment. In the intention-to-treat analysis, there was no evidence of a difference in the proportion of participants with mRS 0-3 at 90 days according to treatment (28 [42%] of 66 patients in the intervention group vs 21 [32%] of 65 in the control group; adjusted odds ratio [OR] 1·74, 95% CI 0·81-3·74). Secondary prespecified analyses of the primary outcome, done to assess the effect of crossovers, showed higher rates of mRS 0-3 at 90 days in patients who actually received the intervention compared with those who received standard medical therapy alone in both per-protocol (28 [44%] of 63 patients with intervention vs 13 [25%] of 51 with standard therapy; adjusted OR 2·90, 95% CI 1·20-7·03) and as-treated (36 [47%] of 77 patients with intervention vs 13 [24%] of 54 with standard therapy; 3·02, 1·31-7·00) populations. The 90-day mortality was similar between groups (22 [33%] of 66 patients in the intervention vs 25 [38%] of 65 in the control group; p=0·54) despite a numerically higher prevalence of symptomatic intracranial haemorrhage in the intervention group. INTERPRETATION: There was no evidence of a difference in favourable outcomes of patients receiving endovascular therapy compared with those receiving standard medical therapy alone. Results might have been confounded by loss of equipoise over the course of the trial, resulting in poor adherence to the assigned study treatment and a reduced sample size due to the early termination of the study. FUNDING: Jiangsu Provincial Special Program of Medical Science.

Lipocalin-2 may produce damaging effect after cerebral ischemia by inducing astrocytes classical activation.

BACKGROUND: Functions of astrocytes in the rehabilitation after ischemic stroke, especially their impacts on inflammatory processes, remain controversial. This study uncovered two phenotypes of astrocytes, of which one was helpful, and the other harmful to anoxic neurons after brain ischemia. METHODS: We tested the levels of inflammatory factors including TNF-a, IL-6, IL-10, iNOS, IL-1beta, and CXCL10 in primary astrocytes at 0 h, 6 h, 12 h, 24 h, and 48 h after OGD, grouped the hypoxia astrocytes into iNOS-positive (iNOS(+)) and iNOS-negative (iNOS(-)) by magnetic bead sorting, and then co-cultured the two groups of cells with OGD-treated neurons for 24 h. We further verified the polarization of astrocytes in vivo by detecting the co-localization of iNOS, GFAP, and Iba-1 on MCAO brain sections. Lentivirus overexpressing LCN2 and LCN2 knockout mice (#024630. JAX, USA) were used to explore the role of LCN2 in the functional polarization of astrocytes. 7.0-T MRI scanning and the modified Neurological Severity Score (mNSS) were used to evaluate the neurological outcomes of the mice. RESULTS: After oxygen-glucose deprivation (OGD), iNOS mRNA expression increased to the peak at 6 h in primary astrocytes, but keep baseline expression in LCN2-knockout astrocytes. In mice with transient middle cerebral artery occlusion (tMCAO), LCN2 was proved necessary for astrocyte classical activation. In LCN2 knockout mice with MCAO, no classically activated astrocytes were detected, and smaller infarct volumes and better neurological functions were observed. CONCLUSIONS: The results indicated a novel pattern of astrocyte activation after ischemic stroke and lipocalin-2 (LCN2) plays a key role in polarizing and activating astrocytes.

Recurrent risk of ischemic stroke due to Vertebrobasilar Dolichoectasia.

BACKGROUND: Patients with vertebrobasilar dolichoectasia usually have persistent hemodynamic abnormalities, and therefore, may bear an increased risk of stroke. This study aimed to identify risk factors for stroke recurrence in patients with vertebrobasilar dolichoectasia. METHODS: Patients with acute ischemic stroke were screened and evaluated for eligibility. Enrolled patients were followed via scheduled clinical visits or telephone interviews. Ischemic stroke recurrence was proposed with clinical symptoms and confirmed with cranial Magnetic Resonance Imaging or Computerized Tomography scans. Baseline characteristics and vascular geometry were compared between patients with and without stroke recurrence. Significant parameters were introduced into COX proportional hazard model to detect possible predictors of stroke recurrence. RESULTS: A total of 115 stroke patients with vertebrobasilar dolichoectasia were enrolled, of which 22 (19.1%) had recurrence during 22 ± 6 months follow-up. Basilar artery diameter ≥ 5.3 mm (HR = 4.744; 95% CI, 1.718-13.097; P = 0.003), diffuse intracranial dolichoectasia (HR = 3.603; 95% CI, 1.367-9.496; P = 0.010) and ischemic heart disease history (HR = 4.095; 95% CI, 1.221-13.740; P = 0.022) had increased risk of recurrence. CONCLUSIONS: Stroke patients with vertebrobasilar dolichoectasia may have a high risk of recurrence. Larger basilar artery diameter or diffuse intracranial dolichoectasia may increase the risk of recurrence.

Emergent loading dose of antiplatelets for stenting after IV rt-PA in acute ischemic stroke: a feasibility study.

BACKGROUND: A loading dose of antiplatelets reduces in-stent thrombosis after stent implantation. However, whether it is safe in patients undergoing acute stenting after intravenous recombinant tissue plasminogen activator (rt-PA) is unclear. METHODS: A case series of acute ischemic stroke patients treated with intravenous rt-PA followed by emergent stenting were prospectively included in Jinling Hospital Stroke Unit. An emergent loading dose of antiplatelets (aspirin 300 mg and clopidogrel 300 mg) were administered to all patients through a nasogastric tube immediately before stenting. Clinical and angiographic outcomes were evaluated in these patients. RESULTS: A total of 12 patients were included. The median of NIHSS score on admission was 15 points (interquartile range 11-19). The median of time from stroke symptom onset to start IV rt-PA and stent placement was 172 min (interquartile range 123.75-189) and 311.5 min (interquartile range 285.5-349.5), respectively. All patients reached complete or partial recanalization (TICI ≥2a). One patient occurred hemorrhagic transformation at 24 h following the emergent loading dose of antiplatelets. A favorable outcome as defined by mRS ≤2 at 90 days was obtained in 58.3% (7/12) of all patients. CONCLUSION: Our finding preliminary suggested that an emergent loading dose of antiplatelets may be safe and feasible for acute stenting after IV rt-PA.

Anterior Borderzone Angle for Hemodynamic Collateral Metric in Patients with Symptomatic Middle Cerebral Artery Stenosis.

BACKGROUND AND AIMS: We aimed to introduce a parameter of anterior borderzone angle (ABZA) to quantitatively evaluate the ACA-MCA leptomeningeal collaterals for middle cerebral artery stenosis (MCAS). METHODS: Two hundred seventy-five patients with 50-100% MCAS and 100 controls were included. The 95% reference range of ABZA was obtained from the controls. ABZAtrans was defined as "ABZA/the 95% upper limit." Relationships between ABZA and MCAS, -ABZAtrans and the TICI grade, the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral grade were analyzed. An ABZA grade model for the ACA leptomeningeal collaterals was tentatively developed. RESULTS: The 95% reference range of ABZA was 0.0º-23.0º. ABZA was significantly associated with MCAS by a function of the fourth power (R2 = 0.723, p < 0.001), and could predict hemodynamic MCAS (≥70%) with an AUC of 0.928 (95% CI 0.903-0.953). ABZAtrans was negatively correlated with the TICI grade (rho = -0.752, p < 0.001) and positively with the ASITN/SIR grade (rho = 0.921, p < 0.001). The ABZA grade was created by rounding -ABZAtrans to a nearest integer, and was closely associated with the ASITN/SIR grade (rho = 0.894, p < 0.001). CONCLUSIONS: ABZA can be used as a hemodynamic parameter to quantitatively evaluate ACA leptomeningeal collaterals.

Risk of Intracranial Hemorrhage after Endovascular Treatment for Acute Ischemic Stroke: Systematic Review and Meta-Analysis.

BACKGROUND: Intracranial hemorrhage is a major complication of endovascular treatment in patients with acute ischemic stroke. Controlled clinical trials reported varied incidences of intracranial hemorrhage after endovascular treatment. This meta-analysis aimed to estimate whether endovascular treatment, compared with medical treatment, increases the risk of intracranial hemorrhage in patients with acute ischemic stroke. METHODS: The current publications on endovascular treatment for acute ischemic stroke were systematically reviewed. Rates of intracranial hemorrhage after endovascular treatment for acute ischemic stroke reported in controlled clinical trials were pooled and analyzed. Random and fixed-effect models were used to pool the outcomes. For analyzing their individual risks, intracranial hemorrhages after endovascular treatment were classified as symptomatic and asymptomatic. RESULTS: Eleven studies involving 1,499 patients with endovascular treatment and 1,320 patients with medical treatment were included. After pooling the data, the risk of any intracranial hemorrhage was significantly higher in patients with endovascular treatment than in patients with medical treatment (35.0 vs. 19.0%, OR = 2.55, 95% CI: 1.64-3.97, p < 0.00001). The risk of asymptomatic intracranial hemorrhage was also significantly higher in patients with endovascular treatment than in those with medical treatment (28 vs. 12%, OR = 3.16, 95% CI: 1.62-6.16, p < 0.001). However, the risks of symptomatic intracranial hemorrhage were similar in patients with endovascular treatment and in those with medical treatment (5.6 vs. 5.2%, OR = 1.09, 95% CI: 0.79-1.50, p = 0.61). CONCLUSION: Although the risk of any intracranial hemorrhage may increase after endovascular treatment, the risk of symptomatic intracranial hemorrhage may remain similar as compared with medical treatment.

Acute basilar artery occlusion: Endovascular Interventions versus Standard Medical Treatment (BEST) Trial-Design and protocol for a randomized, controlled, multicenter study.

Rationale Endovascular treatment plus standard medical therapy is superior to standard medical therapy alone for acute anterior proximal intracranial large artery occlusion strokes. The benefit of endovascular treatment in acute ischemic stroke caused by basilar artery occlusion remains unproven. Aim This study compares the safety and efficacy of endovascular treatment plus standard medical therapy versus standard medical therapy alone in acute ischemic stroke due to basilar artery occlusion. Design The study is a multicenter randomized control trial with blinded outcome assessment. A projected total 344 subjects with acute basilar arterial occlusion within 8 h of estimated occlusion time will be enrolled over three years in China. Patients will be assigned to endovascular treatment plus standard medical therapy and standard medical therapy alone group in 1:1 ratio for study centers. Study outcomes The primary outcome measure is a favorable functional outcome, defined as a modified Rankin Score of 0-3 at 90 days. The primary safety measure is mortality at 90 days. Trial registration ClinicalTrials.gov (NCT 02441556). Summary The BEST trial will provide valuable insights into the safety and efficacy of endovascular treatment for acute ischemic stroke patients with basilar artery occlusion.

Prediction of favorable outcome by percent improvement in patients with acute ischemic stroke treated with endovascular stent thrombectomy.

Our objective was to investigate a method for assessing early improvement and its predictive value for 3-month functional outcome in patients treated with EST. A total of 97 consecutive AIS patients undergoing EST were prospectively collected and retrospective reviewed. Data on demographics, vascular risk factors, admission National Institutes of Health Stroke Scale (NIHSS) score, 24-h NIHSS score, reperfusion and collateral formation were collected. Percent improvement was defined as ([baseline NIHSS score-24-h NIHSS score]/baseline NIHSS score×100%), while absolute improvement was calculated by the difference between scores (baseline NIHSS score-24-h NIHSS score). A 3-month functional outcome was assessed using the modified Rankin Scale (mRS). Favorable outcome was defined as a mRS score of 0-2. Areas under the receiver-operating characteristic (ROC) curve (AUC) for percent improvement and absolute improvement in predicting favorable outcome was compared. Finally, we investigated the independent predictors of improvement at 24h after EST and its relationship with favorable outcome. Pairwise comparison of ROC curves revealed that percent improvement had larger AUC than absolute improvement (p=0.004). Rapid neurological improvement (RNI), defined as percent improvement ⩾30%, was a powerful predictor of favorable outcome (odds ratio [OR] 7.63, confidence interval [CI]: 2.65-21.96; p<0.001). Good collaterals (OR 2.86; 95% CI: 1.11-7.38; p=0.030) and short onset-to-reperfusion time (ORT) (OR 3.02, 95% CI: 1.17-7.80; p=0.022) were independent predictors of RNI. RNI predicted 3-month favorable outcome in AIS patients treated with EST. Good collaterals and short ORT are independent predictors of RNI.

Lack of improvement following endovascular therapy in patients with acute ischemic stroke.

BACKGROUND: Recent randomized trials have consistently demonstrated a clinical benefit of endovascular therapy (ET) over best medical therapy (including intravenous (IV) thrombolysis in eligible patients) or IV thrombolysis only in selected patients with acute ischemic stroke (AIS) due to proximal occlusion in the carotid territory. Previous study demonstrates that lack of improvement (LOI) at 24 hours is an independent predictor of poor outcome and death at 3 months in patients with AIS treated with IV alteplase. However, LOI at 24 hours following ET has not been studied systematically. The purpose of this study is to identify predictors of LOI at 24 hours in patients with AIS after ET as well as the relationship between LOI and unfavorable outcome at 3 months. METHODS: A total of 98 consecutive patients with AIS treated with ET in two separate stroke centers from 2010 to 2014 were retrospectively reviewed. Data on demographics, preexisting vascular risk factors, occlusion site, pre- and post-treatment modified Treatment in Cerebral Ischemia (mTICI) classification, collaterals and National Institutes of Health Stroke Scale (NIHSS) score on admission as well as 24 hours after the endovascular procedurals were collected. LOI was defined as a reduction of 3 points or less on the NIHSS at 24 hours compared with baseline. A 3-month functional outcome was assessed using the modified Rankin scale (mRS). Unfavorable outcome was prespecified as a score of more than 2 on the mRS. The onset-to-reperfusion time (ORT) was defined as time to mTICI 2b or 3 or end of procedure. Long ORT was defined as time to reperfusion beyond 6 hours. Poor reperfusion was defined as mTICI ≦2a. The pretreatment collateral circulation extent was graded as poor (grades 0-1) or good (grades 2-4). RESULTS: Among the 98 patients with AIS who were treated with ET, LOI was present in 48 (49%) subjects. Multivariate analysis indicated that poor collaterals (odds ratio [OR] 3.25; 95% confidence interval [CI]: 1.29-8.19; p = 0.012) and long ORT (OR 3.97, 95% CI: 1.66-9.54; p = 0.002) were independent predictors of LOI. LOI (OR 7.18, 95% CI: 2.39-21.61; p < 0.001) was independently associated with unfavorable outcome at 3 months. CONCLUSION: Among patients with AIS treated with ET, as an independent predictor of unfavorable outcome, LOI at 24 hours is associated with poor collaterals and long ORT.

Correlation study between small vessel disease and early neurological deterioration in patients with mild/moderate acute ischemic stroke.

AIMS: Cerebral small vessel disease (SVD) refers to a group of pathological processes that affect small arteries, arterioles, venules, and capillaries of the brain. We hypothesized that imaging markers of SVD could be associated with neurological deterioration during acute phase of mild/moderate ischemic stroke. METHODS: We performed a prospective cohort with 687 consecutive patients with acute ischemic stroke and also with admission NIHSS score below 12 points. Imaging markers of SVD include silent lacunar infarction, deep cerebral microbleeds (CMBs), brain atrophy, periventricular and semiovale white matter hyperintensities, basal ganglia and semiovale enlarged perivascular spaces as well as SVD burden rating scale, which were evaluated and calculated, respectively. Early neurology deterioration (END) was defined as an increment of NIHSS score ≥2 points in the first 72 h after admission. RESULTS: None of these imaging markers and rating scale of SVD significantly correlated with END after adjusted for major confounders. Post hoc analysis indicated similar negative results in different age, TOAST classification and infarction location subgroups. Only silent infarction (OR 2.42, 95%CI 1.33-5.10) and deep CMBs (OR 2.10, 95%CI 1.08-3.72) seemed to be predictors for END in female patients. However, due to the increased type I error in multiple comparisons, these relationships should not be regarded as statistically significant. CONCLUSION: In patients with mild/moderate acute ischemic stroke, imaging markers of SVD did not correlate with END.

Fluid-Attenuated Inversion Recovery Vascular Hyperintensity Topography, Novel Imaging Marker for Revascularization in Middle Cerebral Artery Occlusion.

BACKGROUND AND PURPOSE: In acute arterial occlusion, fluid-attenuated inversion recovery vascular hyperintensity (FVH) has been linked to slow flow in leptomeningeal collaterals and cerebral hypoperfusion, but the impact on clinical outcome is still controversial. In this study, we aimed to investigate the association between FVH topography or FVH-Alberta Stroke Program Early CT Score (ASPECTS) pattern and outcome in acute M1-middle cerebral artery occlusion patients with endovascular treatment. METHODS: We included acute M1-middle cerebral artery occlusion patients treated with endovascular therapy (ET). All patients had diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery before ET. Distal FVH-ASPECTS was evaluated according to distal middle cerebral artery-ASPECT area (M1-M6) and acute DWI lesion was also reviewed. The presence of FVH inside and outside DWI-positive lesions was separately analyzed. Clinical outcome after ET was analyzed with respect to different distal FVH-ASPECTS topography. RESULTS: Among 101 patients who met inclusion criteria for the study, mean age was 66.2±17.8 years and median National Institutes of Health Stroke Scale was 17.0 (interquartile range, 12.0-21.0). FVH-ASPECTS measured outside of the DWI lesion was significantly higher in patients with good outcome (modified Rankin Scale [mRS] score of 0-2; 8.0 versus 4.0, P<0.001). Logistic regression demonstrated that FVH-ASPECTS outside of the DWI lesion was independently associated with clinical outcome of these patients (odds ratio, 1.3; 95% confidence interval, 1.06-1.68; P=0.013). FVH-ASPECTS inside the DWI lesion was associated with hemorrhagic transformation (odds ratio, 1.3; 95% confidence interval, 1.04-1.51; P=0.019). CONCLUSIONS: Higher FVH-ASPECTS measured outside the DWI lesion is associated with good clinical outcomes in patients undergoing ET. FVH-ASPECTS measured inside the DWI lesion was predictive of hemorrhagic transformation. The FVH pattern, not number, can serve as an imaging selection marker for ET in acute middle cerebral artery occlusion.

Dynamic change of neutrophil to lymphocyte ratio and hemorrhagic transformation after thrombolysis in stroke.

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) has been shown to predict short- and long-term outcomes in ischemic stroke patients. We sought to explore the temporal profile of the plasma NLR in stroke patients treated with intravenous thrombolysis (IVT) and its relationship with intracranial bleeding complications after thrombolysis. METHODS: A total of 189 ischemic stroke patients were prospectively enrolled. Blood samples for leukocyte, neutrophil, and lymphocyte counts were obtained at admission and at 3-6, 12-18, and 36-48 h after IVT. Head CT was performed on admission and repeated after 36-48 h, and a CT scan was done immediately in case of clinical worsening. Hemorrhagic events were categorized as symptomatic intracranial hemorrhage (sICH) and parenchymal hematomas (PH) according to previously published criteria. RESULTS: An increasing trend in the NLR was observed after stroke, and the NLR was higher in patients who developed PH or sICH at 3-6, 12-18, and 36-48 h after IVT (P < 0.01) than in those without PH or sICH. The optimal cutoff value for the serum NLR as an indicator for auxiliary diagnosis of PH and sICH was 10.59 at 12-18 h. Furthermore, the NLR obtained at 12-18-h post-treatment was independently associated with PH (adjusted odds ratio [OR] 1.14) and sICH (adjusted OR 1.14). In addition, patients with a NLR ≥10.59 had an 8.50-fold greater risk for PH (95 % confidence interval [CI] 2.69-26.89) and a 7.93-fold greater risk for sICH (95 % CI 2.25-27.99) than patients with a NLR <10.59. CONCLUSIONS: NLR is a dynamic variable, and its variation is associated with HT after thrombolysis in stroke patients.

Predictors for vascular cognitive impairment in stroke patients.

BACKGROUND: Around two thirds stroke patients may suffer from vascular cognitive impairment (VCI). Our previous study has validated the NINDS-CSN harmonization standard for VCI diagnosis in Chinese. In this study, we aimed to investigate the predictors for VCI in Chinese post-stroke patients. METHODS: We compared epidemiological, clinical, and neuroimaging data (number, size and location of acute infarcts and lacunes, severities of white matter hyperintensities and brain atrophy) between stroke patients with and without VCI. Univariate and logistic regression analyses were utilized to determine VCI predictors. RESULTS: Fifty-six consecutive patients (age, 63.8 ± 8.3 years; female, 37.5%) were recruited at a mean interval of 7.1 months after stroke onset, and 31 (55.4%) patients were diagnosed with VCI based on a validated 60-min neuropsychological battery. VCI patients were older (p = 0.023), less educated (p = 0.001), more likely to be female (p < 0.001), had a recurrent stroke (p = 0.028), and described higher apathy (p = 0.022) and worse pre-stroke cognition (p = 0.048) than cognitively normal patients. Lower educational level (adjusted odds ratio [OR] 0.750, 95% confidence interval [CI], 0.573-0.981; p = 0.035), female sex (adjusted OR 8.288, 95% CI, 1.522-45.113; p = 0.014), recurrent stroke (adjusted OR 11.327, 95% CI, 1.335-96.130, p = 0.026), and global cortical atrophy (adjusted OR 5.730, 95% CI, 1.128-29.101, p = 0.035) were independently associated with VCI in post-stroke patients. CONCLUSIONS: Lower education, female sex, recurrent stroke and global cortical atrophy were associated with VCI in Chinese stroke patients.

Total time of operation is a risk factor of stroke-associated pneumonia in acute ischemic stroke patients with intra-arterial treatment.

BACKGROUND AND PURPOSE: Stroke-associated pneumonia (SAP) is associated with poor functional outcome in patients with acute ischemic stroke (AIS). The objective of this study was to identify predictors of SAP in patients underwent intra-arterial treatment (IAT). METHODS: Consecutive patients with AIS within 6 h from the symptom onset underwent IAT were enrolled. Independent predictors of in-hospital SAP after AIS were obtained using multivariable logistic regression. Kaplan-Meier survival curves were calculated and compared by the log-rank test. RESULTS: Of 165 patients with AIS in the study period, 102 (61.8%) underwent IAT. Twenty-two (21.6%; 95% confidence interval [CI], 14.7-29.4) experienced SAP. Patients with SAP were older (69.2 vs 62.9 years, respectively; P = 0.011), more severely affected (National Institutes of Health Stroke Scale score, 18 vs 9, respectively; P = 0.004), more likely to underwent symptom of dysphagia (86.4% vs 15%, respectively; P < 0.001), lower Glasgow Coma Scale score (9 vs 13, respectively; P < 0.001), and longer operation time (149.5 vs 123, respectively; P < 0.001) than those without SAP. Only symptom of dysphagia (adjust odds ratio [OR], 12.051; 95% CI, 3.457-50.610; P < 0.001) and total time of operation (adjust OR, 1.040; 95% CI, 1.009-1.071; P < 0.001) were identified as independent predictors of SAP. Patients with SAP had stable or improved deficits after AIS with IAT (P < 0.001). CONCLUSIONS: Besides dysphagia, total time of operation is a risk factor of SAP in patients with AIS with IAT.

Lower Serum Caveolin-1 Is Associated with Cerebral Microbleeds in Patients with Acute Ischemic Stroke.

Caveolin-1 (Cav-1) plays pivotal roles in the endothelial damage following stroke. The present study aimed to investigate whether serum Cav-1 level is associated with the presence of cerebral small vessel disease (cSVD) in patients with acute ischemic stroke. To this end, 156 patients were consecutively enrolled. Cranial magnetic resonance imaging was analyzed to determine the surrogates of cSVD, including cerebral microbleeds (CMBs), silent lacunar infarcts (SLIs), and white matter hyperintensities (WMHs). After adjusting for potential confounders, patients with low Cav-1 level had a higher risk of CMBs than patients with high Cav-1 level (OR: 4.05, 95% CI: 1.77-9.30). However, there was no relationship between Cav-1 and the presence of SLIs or WMHs. When CMBs were stratified by location and number, a similar association was found in patients with deep or infratentorial CMBs (OR: 4.04, 95% CI: 1.59-10.25) and with multiple CMBs (OR: 3.18, 95% CI: 1.16-8.72). These results suggest lower serum Cav-1 levels may be associated with CMBs, especially those that are multiple and located in deep brain or infratentorial structures, in patients with acute ischemic stroke. Cav-1 may be involved in the pathophysiology of CMBs, and may act as a potential target for treating cSVD.

Tissue Kallikrein Prevents Restenosis After Stenting of Severe Atherosclerotic Stenosis of the Middle Cerebral Artery: A Randomized Controlled Trial.

In-stent restenosis (ISR) following intracranial artery stenting affects long-term clinical outcome. This randomized controlled trial sought to identify the long-term efficacy of exogenous tissue kallikrein (TK) for preventing ISR after intracranial stenting of symptomatic middle cerebral artery (MCA) atherosclerotic stenosis.Sixty-one patients successfully treated with intracranial stenting for symptomatic MCA M1 segment stenosis (>70%) were enrolled and randomized into 2 groups: control group and TK group. Patients in the TK group received human urinary kallidinogenase for 7 days, followed by maintenance therapy of pancreatic kallikrein for 6 months. The primary end point was angiographically verified ISR at 6 months, and secondary end points included vascular events and death within 12 months. Endogenous TK plasma concentrations of patients were measured before stenting and at the 6-month follow-up time-point.Patients in the TK group had lower occurrence rates of ISR and vascular events than patients in the control group. There was no difference in endogenous TK levels in plasma at 6 months postoperatively between the TK and control groups. Further subgroup analysis revealed that patients without ISR had higher endogenous TK levels at baseline and lower concentrations at 6 months postoperatively compared with patients who underwent ISR.Exogenous TK is effective for the prevention of ISR after intracranial stenting.