Outcome and Risk of Poststroke Pneumonia in Patients with Acute Ischemic Stroke After Endovascular Thrombectomy: A Post Hoc Analysis of the DIRECT-MT Trial.

BACKGROUND: In this study, we aimed to investigate the risk factors and impact of poststroke pneumonia (PSP) on mortality and functional outcome in patients with acute ischemic stroke (AIS) after endovascular thrombectomy (EVT). METHODS: This was a post hoc analysis of a prospective randomized trial (Direct intraarterial thrombectomy in order to revascularize AIS patients with large-vessel occlusion efficiently in Chinese tertiary hospitals: a multicenter randomized clinical trial). Patients with AIS who completed EVT were evaluated for the occurrence of PSP during the hospitalization period and their modified Rankin Scale (mRS) scores at 90 days after AIS. Logistic regression analysis was conducted to investigate the independent predictors of PSP. Propensity score matching was conducted for the PSP and non-PSP groups by using the covariates resulting from the logistic regression analysis. The associations between PSP and outcomes were analyzed. The outcomes included 90-day poor functional outcome (mRS scores > 2), 90-day mortality, and early 2-week mortality. RESULTS: A total of 639 patients were enrolled, of whom 29.58% (189) developed PSP. Logistic regression analysis revealed that history of chronic heart failure (unadjusted odds ratio [OR] 2.011, 95% confidence interval [CI] 1.026-3.941; P = 0.042), prethrombectomy reperfusion on initial digital subtraction angiography (OR 0.394, 95% CI 0.161-0.964; P = 0.041), creatinine levels at admission (OR 1.008, 95% CI 1.000-1.016; P = 0.049), and National Institutes of Health Stroke Scale at 24 h (OR 1.023, 95% CI 1.007-1.039; P = 0.004) were independent risk factors for PSP. With propensity scoring matching, poor functional outcome (mRS > 2) was more common in patients with PSP than in patients without PSP (81.03% vs. 71.83%, P = 0.043) at 90 days after EVT. The early 2-week mortality of patients with PSP was lower (5.74% vs. 12.07%, P = 0.038). But there was no statistically significant difference in 90-day mortality between the PSP group and non-PSP group (22.41% vs. 14.94%, P = 0.074). The survivorship curve also shows no statistical significance (P = 0.088) between the two groups. CONCLUSIONS: Nearly one third of patients with AIS and EVT developed PSP. Heart failure, higher creatinine levels, prethrombectomy reperfusion, and National Institutes of Health Stroke Scale at 24 h were associated with PSP in these patients. PSP was associated with poor 90-day functional outcomes in patients with AIS treated with EVT.

Pentraxin-3 in Thrombolytic Therapy for Acute Ischemic Stroke: No Relation with Curative Effect and Prognosis.

BACKGROUND Pentraxin-3 (PTX3) is considered a high quality inflammatory marker of the severity and prognosis of several diseases, however, the value of PTX3 in thrombolytic therapy for acute ischemic stroke remains unclear and PTX3 is still controversial in evaluating the prognosis of stroke patients. In this study, we investigated the association of PTX3 with thrombolytic therapy in patients with acute ischemic stroke. MATERIAL AND METHODS Forty-seven stroke patients who received thrombolytic therapy within 4.5 hours after symptom onset were enrolled consecutively between July 2016 and June 2017. All the patients underwent multiphase CTA (computerized tomography angiography) or CT perfusion before thrombolysis with no indication for endovascular treatment. Initial and 24 hours of National Institute of Health Stroke Scale (NIHSS) scores and serum PTX3 level, stroke risk factors and predictors, and mRS (modified Rankin scale) at 3 months were collected prospectively. Predictors of thrombolytic therapy effect and long-term prognosis were investigated by univariate and multivariate logistic regression. RESULTS The 24 hour NIHSS score and the treatment time was associated with symptom improvement, while the PTX3 level had no association with neurological improvement and prognosis in stroke patients receiving thrombolytic therapy. CONCLUSIONS PTX3 is not suitable to serve as an indicator of thrombolytic efficacy and had no association with long-term prognosis in stroke patients receiving thrombolytic therapy.

Clinical Study of Intracranial and Extracranial Atherosclerotic Stenosis in Spontaneous Intracerebral Hemorrhage Patients.

BACKGROUND AND PURPOSE: Nowadays, researchers had begun to focus on the use of antiplatelet and statins in patients with spontaneous intracerebral hemorrhage (sICH), but atherosclerosis treatment remains uncertain in these patients. We aimed to investigate the incidence and characteristics of intracranial and extracranial atherosclerotic stenosis in these patients and analyze its related risk factors. METHODS: Intracranial and extracranial arteries of consecutive patients with sICH were studied retrospectively with computed tomography angiography of head and neck. The risk factors, severity, and distribution of atherosclerotic stenosis were examined and analyzed. RESULTS: We included 226 patients with sICH, of whom 110 patients (48.7%) had atherosclerotic stenosis. Of the patients, 57 (51.8%) had intracranial stenosis and 75 (68.2%) had multiple stenosis. A total of 1870 vessels were examined and 287 vessels (15.3%) had atherosclerotic stenosis, of which 217 cases (75.6%) were mild stenosis. Intracranial and extracranial atherosclerosis was more likely to be found in patients with advanced age (P < .001), diabetes mellitus (P = .008), non-deep hemorrhage (P = .011). CONCLUSIONS: Atherosclerotic stenosis is common in patients with sICH, and is characterized by mild stenosis and the involvement of multiple sites. The stenosis of the vertebrobasilar system is relatively severe. Advanced age, diabetes mellitus, and non-deep bleeding are its related risks.

Decreased levels and function of circulating endothelial progenitor cells in unruptured intracranial saccular aneurysm patients.

Circulating endothelial progenitor cells (EPCs) play a critical role in maintaining endothelial integrity and keeping vascular homeostasis. Previously, we reported that EPCs were involved in repair and remodeling of aneurismal wall. In the present study, we verified this hypothesis by investigating the proliferative ability and count of EPCs in peripheral blood of patients with unruptured intracranial aneurysms (UIAs). Twenty-four patients with UIAs (UIA group) and 24 negative controls (control group) were included in this study. Peripheral blood monocytes (PBMCs) were harvested and selectively cultured. The colony-forming ability of cultured cells was analyzed and the biological functions were examined by testing the adsorption of ulex europaeus agglutinin-1 labeled by fluorescein isothiocyanate and acetylated low-density lipoprotein internalization. The migratory and adhesive ability of cultured EPCs were assessed. In vitro cultured PBMCs were identified as EPCs by examining surface markers CD34, CD133 and vascular endothelial growth factor receptor 2 using flow cytometry. EPCs from UIA group possessed significantly decreased proliferative, migratory and adhesive capacities compared with EPCs from control group. Furthermore, EPCs count in UIA group was significantly decreased. Collectively, these results indicated that the circulating EPCs of UIA patients may be involved in intracranial aneurysm repair and remodeling.

Patient-Reported Anxiety/Depression After Endovascular Thrombectomy: A post-hoc Analysis of Direct-MT Trial.

OBJECTIVE: To analyze the effect of endovascular thrombectomy (EVT) alone vs. EVT after an intravenous (IV) alteplase of ischemic stroke on a patient-reported anxiety/depression, and to identify predictors of patient-reported anxiety/depression by analyzing data from Direct Intraarterial Thrombectomy in Order to Revascularize the patients with Acute Ischemic Stroke with a Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals: a Multicenter Randomized Clinical Trial (DIRECT-MT). METHODS: Patients with acute ischemic stroke (AIS), triggered by a large-vessel occlusion in the anterior circulation, were randomly allocated to undergo an EVT after IV alteplase (combination-therapy group) or an EVT alone (EVT-alone group) at a 1:1 ratio in DIRECT-MT. Patients in both groups were followed up for 90 days (±14 days) after stroke using a structured modified Ranking Scale (mRS), a Barthel Index (BI), and a 5-Dimensional European Quality of Life Scale (EQ-5D-5L). Patients who returned EQ-5D-5L were included. The EQ-5D-5L anxiety/depression dimension was used to analyze the patient-reported anxiety/depression. First, differences in patient-reported anxiety/depression were compared between the combination-therapy group and the EVT-alone group. Then, the baseline and influencing factors between the anxiety/depression group and no anxiety/depression group were analyzed using univariate regression analysis. Finally, variables with p < 0.1 in univariate regression were subjected to multivariable binary regression analysis to screen independent predictors for patient-reported anxiety /depression after ischemic stroke. RESULTS: : Five hundred fifteen patients returned the EQ-5D-5L in Direct-MT. Of these patients, 226 (43.88%) reported a level of anxiety/depression, and about 7% reported a severe or extremely severe anxiety/depression. The patient-reported anxiety/depression in the EVT-alone group was significantly higher than that in the combination-therapy group (48.26% vs. 39.45%, p = 0.04). The clinical outcomes were significantly different between the no Anxiety/Depression Group and the anxiety/depression group (mRS at 90 days:2 vs 3, p < 0.001; BI of 95 or 100 at 90 days: 73.36% vs 42.04%, p < 0.001; EQ-5D-5l utility indexes at 90 days:0.96 vs.57, p < 0.001). Logistic regression analysis showed that allocation to thrombolysis before EVT strategy was inversely associated with anxiety/depression [0.61(0.40, 0.94), p = 0.03], an insular cortex ischemia, and National Institute of Health Strocke Scale (NIHSS) at 7 days were positively associated with anxiety/depression [2.04(1.07, 3.90), p = 0.03; 1.07(1.03, 1.12), p < 0.001]. CONCLUSIONS: Patient-reported anxiety/depression may suggest that there is a benefit to administering intravenous alteplase before EVT. It may also indicate that it is better to provide IV alteplase before EVT, rather than EVT alone according to patient-reported anxiety/depression. Future research should consider not only the motor function impairments but also the patient-reported mental problems as measures of treatment efficacy in patients with stroke (DIRECT-MT ClinicalTrials.gov number, NCT03469206).

Naoxintong Capsule for Secondary Prevention of Ischemic Stroke: A Multicenter, Randomized, and Placebo-Controlled Trial.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION: The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).

[Flavonoids of puerarin versus tanshinone II A for ischemic stroke: a randomized controlled trial].

BACKGROUND: Flavonoids are widely used today in the treatment of ischemic stroke. The therapeutic effects and functions of flavonoids are, therefore, generating more and more interest. OBJECTIVE: To investigate the therapeutic effects and functions of flavonoids of puerarin in treating patients with ischemic stroke. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 67 inpatients suffering from ischemic stroke from the Department of Neurology, Changhai Hospital in China were divided into two groups randomly, the treatment group, which was treated with flavonoids of puerarin, and the control group, administered with tanshinone II A sulfate instead. MAIN OUTCOME MEASURES: Defects in neurological function were evaluated according to the National Institutes of Health Stroke Scale (NIHSS) on the first day of onset. Lactate dehydrogenase (LDH), serum interleukin-6 (IL-6) and brain-derived neurotrophic factor (BDNF) levels were determined by radioimmunoassay on the second trial day. After a 14-day treatment, LDH, serum IL-6 and BDNF levels and NIHSS score were also detected, and CT perfusion imaging was used to measure and analyze the regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) and mean transit time (MTT). RESULTS: On the first day, NIHSS scores of the two groups were similar. On the second day there was no significant difference in LDH and IL-6 levels between the treatment group and the control group. After a 14-day treatment, LDH and IL-6 levels and the NIHSS score in the treatment group were lower than those in the control group (P<0.05). There was no significant difference in BDNF levels in the two groups. After 14 d, the CT perfusion imaging demonstrated that the treatment group showed more effective blood perfusion than the control group. CONCLUSION: Flavonoids of puerarin can restrain the increase of IL-6 after acute ischemic stroke, and depress the LDH raised by reperfusion after cerebral ischemia. It can also enhance blood perfusion of the ischemic region.

Higher Baseline Cortical Score Predicts Good Outcome in Patients With Low Alberta Stroke Program Early Computed Tomography Score Treated with Endovascular Treatment.

BACKGROUND: Patients with large vessel occlusion and noncontrast computed tomography (CT) Alberta Stroke Program Early CT Score (ASPECTS) <6 may benefit from endovascular treatment (EVT). There is uncertainty about who will benefit from it. OBJECTIVE: To explore the predicting factors for good outcome in patients with ASPECTS <6 treated with EVT. METHODS: We retrospectively reviewed 60 patients with ASPECTS <6 treated with EVT in our center between March 2018 and June 2019. Patients were divided into 2 groups because of the modified Rankin Score (mRS) at 90 d: good outcome group (mRS 0-2) and poor outcome group (mRS ≥3). Baseline and procedural characteristics were collected for unilateral variate and multivariate regression analyses to explore the influent variates for good outcome. RESULTS: Good outcome (mRS 0-2) was achieved in 24 (40%) patients after EVT and mortality was 20% for 90 d. Compared with the poor outcome group, higher baseline cortical ASPECTS (c-ASPECTS), lower intracranial hemorrhage, and malignant brain edema after thrombectomy were noted in the good outcome group (all P < .01). Multivariate logistic regression showed that only baseline c-ASPECTS (≥3) was positive factor for good outcome (odds ratio = 4.29; 95% CI, 1.21-15.20; P = .024). The receiver operating characteristics curve indicated a moderate value of c-ASPECTS for predicting good outcome, with the area under receiver operating characteristics curve 0.70 (95% CI, 0.56-0.83; P = .011). CONCLUSION: Higher baseline c-ASPECTS was a predictor for good clinical outcome in patients with ASPECTS <6 treated with EVT, which could be helpful to treatment decision.

Association of CYP2J2 gene polymorphisms with ischemic stroke and stroke subtypes in Chinese population.

BACKGROUND AND PURPOSE: Ischemic stroke (IS) is the main cause of mortality and disability among the old people in China and is a multifactorial disease influenced by many factors including genetic factors like the allele for CYP 2J2. It has been demonstrated that CYP2J2 polymorphisms alter the transcriptional activity. However, studies on the association between CYP2J2-50G/T polymorphism and IS have reported conflicting results. Thus, our study aimed to examine the association between 4 variants in the CYP2J2 gene and the risk of IS and its subtypes, in the Chinese population. MATERIALS AND METHODS: In this study, genotyping was performed by using polymerase chain reaction (PCR) sequencing for 202 IS patients and 206 age- and sex-matched controls. Odds ratios (ORs) and confidence interval (CI) were estimated by multivariate logistic regression and PCR results were confirmed by DNA sequencing. A meta-analysis was conducted to evaluate the association of CYP2J2-50G>T polymorphism with the risk of IS in Chinese population by calculating pooled OR. RESULTS: We found this polymorphism was significantly associated with IS (17.82% vs. 10.68%, P = 0.039). Multiple logistic regression analysis revealed that GT genotype was associated with a significantly high risk of IS (OR = 2.32, 95% CI: 1.21-4.45, P = 0. 011) after adjustment for other confounding factors such as hypertension, diabetes, heart disease, smoking habit, family history, triglyceride and low-density lipoprotein levels. We also found a significant association of GT genotype with small artery occlusion (SAA) (P < 0.05; OR = 2.22; 95% CI: 1.043-4.72). Meta-analysis results also showed that the GT genotype carriers had a negative effect on the risk of IS in Chinese population with overall OR of 1.40 (95% CI: 1.06-1.84). CONCLUSION: The findings of the present study suggested that polymorphism in -50G/T position of CYP2J2 gene might be a risk factor for IS in Chinese population. Further large prospective studies were required to confirm these findings.

Effect of Baseline Characteristics on the Outcome of Stent Retriever-Based Thrombectomy in Acute Basilar Artery Occlusions: A Single-Center Experience and Pooled Data Analysis.

OBJECTIVES: To explore the association of baseline characteristics and the outcome of patients with acute basilar artery occlusion (BAO) after stent retriever-based thrombectomy (SRT). METHODS: Clinical and imaging information of consecutive SRT-treated patients with BAO from a comprehensive stroke center and up-to-date literature were reviewed respectively. The impact of baseline variables toward favorable outcome was evaluated using subgroup analysis and odds ratio (OR) extracted from published data together with single-center records using pooled analysis. RESULTS: Nineteen cases from our center and 15 published studies involving 487 cases were included. Estimated pooled favorable outcome rate was 0.3746 (95% confidence interval [CI], 0.3165-0.4327), mortality was 0.2950 (95% CI, 0.2390-0.3510). Pooled estimates showed that successful reperfusion (modified thrombolysis in cerebral ischemia scale 2b or 3) gained by SRT alone was 0.7317 (95% CI, 0.6532-0.8102) and final successful reperfusion rate with or without additional reperfusion procedures was 0.8834 (95% CI, 0.8279-0.9390). Univariate analysis indicated that patients with successful reperfusion (OR, 2.05; P = 0.05), distal segment occlusion (OR, 2.03; P = 0.03), and cardioembolus origin (OR, 2.13; P = 0.01) were more likely to have favorable outcome (modified Rankin Scale score ≤2 at 3 months). Study series that applied intra-arterial thrombolysis, angioplasty, or stenting as rescuing therapy had higher successful reperfusion rate but they did not show a higher rate of favorable outcome. CONCLUSIONS: SRT with or without additional treatment appeared to be effective for the treatment of BAO. Successful reperfusion, distal segment occlusion, and cardiac embolism were associated with favorable outcome. The overall benefit of lesions requiring additional reperfusion therapy was unclear.

[Endovascular stent-assisted angioplasty for atherosclerotic intracranial stenosis, a clinical analysis of 39 cases].

OBJECTIVE: To assess the preliminary outcome of endovascular stent-assisted angioplasty for intracranial stenosis. METHODS: Thirty-nine patients with atherosclerotic intracranial stenosis (19 cases in posterior circulation and 20 in anterior circulation) were treated with endovascular angioplasty using balloon-expandable coronary stents. Follow-up was made for 4 - 24 months. The clinical manifestations were observed and CT, MR, or DSA were conducted before and after the operation. RESULTS: All of the stents were successfully implanted on the first procedure without procedural and periprocedural complications. The mean carotid artery stenosis rate was 73.5 +/- 6.7% before the procedure and 11.2 +/- 4.3% after the procedure. The patients were clinical asymptomatic and neurologically intact. Follow-up angiographies made in 29 patients revealed no restenosis. CONCLUSION: With effective short-term results and helpful in decreasing incidence of stroke, endovascular stenting is safe and feasible for treatment of intracranial stenosis.

CD40 ligand as a potential biomarker for atherosclerotic instability.

OBJECTIVE: The signaling protein CD40 and its ligand, CD40L, are thought to contribute to atherosclerotic plaque formation and rupture. We sought to determine their utility as markers of cerebral atherosclerosis and neurological dysfunction. METHODS: We recruited 82 patients with acute cerebral infarction (ACI) and classified each as having large-artery atherosclerosis (LAA, 30), small-artery occlusion (36), or cardioaortic embolism (16). We also recruited 17 patients who had carotid artery stenosis (CAS) without stroke and 20 healthy individuals as controls. CD40L expression on peripheral blood monocytes (PBMCs) was detected by direct immunofluorescence with flow cytometry, and serum soluble CD40L (sCD40L) was measured by ELISA. RESULTS: CD40L expression on PBMCs was highest in the LAA group, followed by that in the CAS group (both P < 0·01 versus control). It was also higher in patients with atherosclerotic infarction than in those without atherosclerosis (P < 0·05). PBMC CD40L expression was sensitive and specific for detecting atherosclerosis and LAA cerebral infarction and was superior to serum C-reactive protein for predicting cerebral atherosclerosis (P < 0·01). Serum sCD40L was higher in patients with ACI than in healthy controls (P < 0·01) or patients with CAS (P < 0·01) and correlated with increased disability on three scales (all P < 0·01). CONCLUSIONS: We conclude that patients with ACI have an upregulated CD40-CD40L system, which could be used as a clinical biomarker for assessing atherosclerotic instability and severity of neurological dysfunction.

Reconstructive Treatment of Ruptured Intracranial Spontaneous Vertebral Artery Dissection Aneurysms: Long-Term Results and Predictors of Unfavorable Outcomes.

INTRODUCTION: Few studies focused on predictors of unfavorable outcomes (modified Rankin Scale, 2-6) after reconstructive treatment of the ruptured intracranial spontaneous vertebral artery dissection aneurysms (ris-VADAs), which was evaluated based on 57 reconstructed lesions in this study. METHODS: Results of 57 consecutive patients (M:F = 29∶28; median age, 48 years; range, 27 to 69 years) harboring 57 ris-VADAs, which were treated with coils combined with single stent(n = 32), double overlapping stents (n = 16), and triple overlapping stents (n = 9) between October 2000 to March 2011, were retrospectively reviewed and analyzed. RESULTS: The available (n = 54) mean durations of angiographic and clinical follow-ups were 27 months (range, 12 to 78) and 62 months (range, 12 to 132), respectively. The involvement of PICA (p = 0.004), size of lesions (p = 0.000), quantity of stent (p = 0.001), and coil type (p = 0.002) affected the immediate obliteration grade, which was only risk factor for angiographic recurrences (p = 0.031). Although the post-treatment outcomes did not differ between single stent and multiple stents (p = 0.434), 5 angiographic recurrences, 1 rebleeding and 1 suspected rebleeding, all occurred in partial obliteration after single-stent-assisted coiling. Progressive thrombosis and in-stent obliteration were not detected on follow-up angiograms. Older age (odds ratio [OR] = 1.090; 95% confidence interval [CI], 1.004-1.184; p = 0.040) and unfavorable Hunt-Hess scale (OR = 4.289; 95%CI, 1.232-14.933; p = 0.022) were independent predictors of unfavorable outcomes in the reconstructed ris-VADAs. CONCLUSIONS: Immediate obliteration grade was only risk factor for angiographic recurrence after reconstructive treatment. Unfavorable Hunt-Hess grade and older age were independent predictors of unfavorable outcomes in ris-VADAs.

Hemichorea-hemiballismus associated with nonketotic hyperglycemia: a possible role of inflammation.

Three cases of hemichorea-hemiballismus (HC-HB) associated with nonketotic hyperglycemia were reported. Of them two patients presented as HC-HB and the remaining one as generalized chorea-ballismus (CB). Brain MRI showed characteristic T1-weighted high-intensity lesions in the contralateral or bilateral striatum without edema or mass effect. They all had a prior history of respiratory or urinary infection. Cerebrospinal fluid test in two patients showed an elevation of protein concentration with normal cell and an increased IgG content and elevated IgG index or 24 h IgG intrathecal synthesis rate. These results suggested that inflammation within the central nervous system may participate in the pathogenesis of chorea and ballismus induced by NKH.