Carotid Siphon Calcification Predicts the Symptomatic Progression in Branch Artery Disease With Intracranial Artery Stenosis-Brief Report.

BACKGROUND: Arterial calcification in the aortic arch, carotid bifurcation, or siphon on computed tomography was associated with cardiovascular disease. The association between arterial calcification prevalence and progression of branch atheromatous disease (BAD) in intracranial artery atherosclerosis was little investigated. METHODS: This study included 310 patients with ischemic stroke from one stroke center. Patients were divided into BAD (110) and non-BAD groups (200). Baseline characteristics, lipids, and arterial calcification were measured. The primary outcome was the prevalence of arterial calcification in BAD progression, and the secondary outcome was the prevalence of calcification in arterial stenosis. The association or correlation among calcification prevalence, lipid markers, and BAD progression was analyzed using logistic regression, receiver operating characteristic curve, and linear regression. RESULTS: Our study found that carotid siphon calcification on computed angiography was more prevalent (P=0.01) in patients with BAD and also more prevalent (P<0.001) in intracranial artery stenosis, and its computed tomography values could independently predict the symptomatic progression (P=0.01). Furthermore, a strong linear correlation between oxidized lipid and calcification density was found (beta=-0.73, P=0.0048) in patients with BAD, a subtype (B-type) of intracranial arterial atherosclerotic disease. CONCLUSIONS: We found that carotid siphon calcification was associated with BAD and its computed tomography values could predict the symptomatic progression in patients with intracranial arterial atherosclerotic disease and BAD, indicating the important role of carotid calcification in B-type intracranial arterial atherosclerotic disease. REGISTRATION: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR1800018315.

Elevated SIRT2 of serum exosomes is positively correlated with diagnosis of acute ischemic stroke patients.

BACKGROUND: Silent Information Regulator 2 (SIRT2) protein inhibition has been shown to play a neuroprotective role in acute ischemic stroke (AIS) in mice. However, its role in AIS patients has not been fully understood. In this study, we aimed to analyze SIRT2 protein expression in serum exosomes of AIS and non-AIS patients, and evaluate its potential role in diagnosis and prognosis of AIS. METHODS: Serum exosomes from 75 non-AIS subjects and 75 AIS patients were isolated. The SIRT2 protein levels in exosomes were analyzed using enzyme linked immunosorbent assay (ELISA). The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the severity of the disease. The modified Rankin Scale (mRS) was employed to assess the functional outcomes of the patients at 3-months following stroke onset. RESULTS: The SIRT2 protein concentration of serum exosomes were higher in AIS patients than non-AIS patients (p < 0.001). Furthermore, the receiver operative characteristic curve (ROC) demonstrated that higher serum exosome SIRT2 could differentiate AIS patients from non-AIS patients with a sensitivity of 81.3% and a specificity of 75.3%. The area under the curve was 0.838 (95% CI: 0.775, 0.902). Additionally, higher SIRT2 concentration of serum exosomes were associated with NIHSS ≥ 4 (p < 0.001) and mRS ≥ 3 (p = 0.025) in AIS patients. The ROC analysis showed SIRT2 could discriminate stroke with NIHSS ≥ 4 from mild stroke (NIHSS < 4) with a sensitivity of 75.0% and a specificity of 69.6%. The area under the curve was 0.771 (95% CI: 0.661,0.881). Similarly, the test showed SIRT2 could differentiate between AIS patients with mRS ≥ 3 from those with mRS < 3 with a sensitivity of 78.3% and a specificity of 51.9%. The area under the curve was 0.663 (95% CI: 0.531,0.796). The logistic regression analysis revealed that SIRT2 concentration in serum exosomes can independently predict the diagnosis of AIS (odd ratio = 1.394, 95%CI 1.231-1.577, p < 0.001) and higher NIHSS scores (≥ 4) (odd ratio = 1.258, 95%CI 1.084-1.460, p = 0.002). However, it could not independently predict the prognosis of AIS (odd ratio = 1.065, 95%CI 0.983-1.154, p = 0.125). CONCLUSION: The elevation of SIRT2 in serum exosomes may be a valuable biomarker of AIS, which may be a potential diagnostic tool to facilitate decision making for AIS patients.

Reduced left hippocampal perfusion is associated with insomnia in patients with cerebral small vessel disease.

OBJECTIVES: Insomnia was associated with cerebral structural changes and Alzheimer's disease. However, associations among cerebral perfusion, insomnia with cerebral small vessel disease (CSVD), and cognitive performance were little investigated. METHODS: This cross-sectional study included 89 patients with CSVDs and white matter hyperintensities (WMHs). They were dichotomized into the normal sleep and poor sleep group, according to Pittsburgh sleep quality index (PSQI). Baseline characteristics, cognitive performance, and cerebral blood flow (CBF) were measured and compared between the two groups. The association or correlation between cerebral perfusion, cognition, and insomnia was analyzed using binary logistic regression. RESULTS: Our study found that declined MoCA score (P = .0317) was more prevalent in those with poor sleep. There was a statistical difference in the recall (P = .0342) of MMSE, the delayed recall (P = .0289) of MoCA between the two groups. Logistic regression analysis showed educational background (P < .001) and insomnia severity index (ISI) score (P = .039) were independently correlated with MoCA scores. Arterial spin labeling demonstrated that left hippocampal gray matter perfusion was significantly reduced (P = .0384) in the group with poor sleep. And, negative correlation was found between left hippocampal perfusion and PSQI scores. CONCLUSIONS: In the patients with CSVDs, insomnia severity was associated with cognitive decline. Left hippocampal gray matter perfusion was correlated with PSQI scores in CSVDs.

Persistent hyperglycemia is a useful glycemic pattern to predict stroke mortality: a systematic review and meta-analysis.

BACKGROUND: Glycemic patterns have been reported to be prognostic factors for stroke; however, this remains to be further evaluated. This meta-analysis aimed to evaluate the usefulness of glycemic patterns such as persistent hyperglycemia (PH) including short duration and long duration PH (SPH; LPH), admission hyperglycemia (AH), short-duration hyperglycemia (SH), and persistent normoglycemia (PN) in predicting stroke prognosis using published results. METHODS: Major scientific databases including but are not limited to PubMed, EMBASE, Web of Science, Ovid, CNKI (Chinese National Knowledge Infrastructure), and Clinicaltrials.gov were searched till 1st March 2021 for clinical trials on the correlation between glycemic patterns and stroke outcomes. The primary outcome was defined as short-term (1- or 3-month) post-stroke mortality, and the secondary outcome was post-stroke hemorrhage at 6 months. RESULTS: Ten studies involving 3584 individuals were included in the final analysis. In subgroup analyses, PH patients with no history of diabetes had increased post-stroke mortality (odds ratio [OR]: 4.80, 95% CI: 3.06-7.54) than patients with no PH; and patients with glucose levels > 140 mg/dl had greater mortality (OR: 5.12, 95% CI: 3.21-8.18) than those with glucose levels < 140 mg/dl; compared with AH patients, PH patients had increased short-term mortality (OR: 0.31, 95% CI: 0.16-0.60). In the prediction of stroke mortality among patients without diabetes, SPH (OR: 0.28, 95%CI: 0.12-0.69) seemed to be more related to increased mortality than LPH (OR: 0.35, 95% CI: 0.14--0.90). CONCLUSIONS: PH, especially SPH, could predict increased post-stroke mortality in non-diabetic patients. The rank of individual glycemic patterns in predicting stroke mortality in non-diabetic patients was SPH > LPH > AH > PN.

Persistent inflammation worsens short-term outcomes in massive stroke patients.

BACKGROUND: Persistent inflammation is an important driver of disease progression and affects prognosis. Some indicators of inflammation predict short-term outcomes. The relationship between prognosis, especially mortality, and persistent inflammation in massive stroke has not been studied, and this has been the subject of our research. METHODS: From April 1, 2017 to February 1, 2020, consecutive patients were prospectively enrolled. Clinical data, laboratory data, imaging data and follow-up infections morbidity were compared between 2 groups according to modified Rankin scale (mRS) scores (mRS < 3 and ≥ 3) at 1 month. The binomial logistic analysis was used to determine independent factors of 1-month prognosis. Short-term functional outcome, mortality and infection rates in massive stroke with and without persistent inflammation were compared. RESULTS: One hundred thirty-nine patients with massive stroke were included from 800 patients. We found that admission blood glucose levels (p = 0.005), proportions of cerebral hemispheric (p = 0.001), posterior circulatory (p = 0.035), and lacunar (p = 0.022) ischemia were higher in poor outcome patients; neutrophil-to-lymphocyte ratio (odd ratio = 1.87, 95%CI 1.14-3.07, p = 0.013) and blood glucose concentrations (odd ratio = 1.34, 95%CI 1.01-1.79, p = 0.043) can independently predict the short-term prognosis in massive stroke patients. We also found that the incidence of pulmonary infection (p = 0.009), one-month mortality (p = 0.003) and adverse outcomes (p = 0.0005) were higher in patients with persistent inflammation. CONCLUSIONS: This study suggested that persistent inflammation is associated with poor prognosis, 1-month mortality and the occurrence of in-hospital pulmonary infection and that higher baseline inflammation level predicts short-term poor outcomes in massive stroke.

Systemic immune-inflammation index (SII) but not platelet-albumin-bilirubin (PALBI) grade is associated with severity of acute ischemic stroke (AIS).

INTRODUCTION: Inflammation plays an important role in stroke. Many inflammatory markers in peripheral blood are proved to be associated with stroke severity or prognosis. But few comprehensive models or scales to evaluate the severity of stroke have been reported. Systemic immune-inflammation index (SII) and platelet-albumin-bilirubin (PALBI) grade as new markers of inflammation have shown their positive association with liver cancer. The relation between SII, or PALBI and stroke remains uncertain. OBJECTIVE: To investigate the relationship between SII, PALBI grade and stroke severity. METHODS: Patients with ischemic stroke with hospital admission <24 h after symptom onset were prospectively included in a stroke registry. Demographic, clinical, and laboratory data were collected immediately after admission in all patients. The National Institutes of Health Stroke Scale (NIHSS) was used to assess stroke severity upon admission. Minor stroke was defined as NIHSS score < =5, moderate-to-severe stroke as NIHSS score >5. SII, calculated as platelet × neutrophil/lymphocyte was divided into four groups according to interquartile range: lowest SII (SII < 353.9 × 109/L), low SII (353.9-532.8 × 109/L), high SII (532.8-783.9 × 109/L), and highest SII (>783.9 × 109/L) group. RESULTS: A total of 362 patients with ischemic stroke were included, and between minor and moderate-to-severe stroke significant difference was found in SII (p < 0.0001), NLR (p < 0.0001), and PLR (p = 0.001), respectively. After multivariate regression analyses, SII groups (Odd ratio = 1.351, 95% confidence interval 1.084-1.684, p = 0.007) not PALBI was an independent risk factor for stroke severity. CONCLUSION: We found that SII but not PALBI, which both are markers of inflammation, was independently associated with stroke severity.

Insulin Resistance is Significantly Related with Worse Clinical Outcomes in Non-Diabetic Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

OBJECTIVES: to investigate the relationship between insulin resistance (IR) and clinical outcomes in non-diabetic ischemic stroke patients treated with intravenous thrombolysis. METHODS: We recruited non-diabetic ischemic stroke patients treated with intravenous thrombolysis prospectively. IR was defined as homeostasis model assessment-estimated insulin resistance index ≥2.80. Initial stroke severity was assessed using the National Institutes of Health Stroke Scale scores, and infarct volume was measured using DWI. Clinical outcomes were evaluated by neurological improvement and hemorrhagic transformation at 24 hours, and favorable functional prognosis at 90 days. RESULTS: 232 patients were enrolled into this study. IR group was 67 patients, non-IR group was 165 patients. Compared with the non-IR group, the probability of neurological improvement at 24 h ours and favorable functional outcome at 90 days in IR group were all significantly lower (41.79% vs 63.03%, p<0.01; 73.13% vs 89.09%, p<0.01 respectively), whereas the ratio of hemorrhagic transformation was much higher (16.42% vs 4.85%, p<0.01). In multivariable logistic regression, IR was negatively associated with neurological improvement and favorable functional prognosis (OR=0.39, 95%CI, 0.20-0.76, p<0.01; OR= 0.26, 95%CI, 0.07-0.91, p=0.04, respectively), but was positively correlated with hemorrhagic transformation (OR=4.07, 95%CI, 1.13-14.59, p=0.03) after adjusting traditional risk factors. We analyzed 108 infarct volume data further, the median of volume in IR group was 2.27 cm3, higher than that in non-IR group (1.96 cm3), but no statistical difference (p=0.65). CONCLUSIONS: In non-diabetic ischemic stroke patients treated with intravenous thrombolysis, IR was related with worse clinical outcomes, but not with infarct volume.

Minimally Invasive Surgery in Patients With Intracerebral Hemorrhage: A Meta-Analysis of Randomized Controlled Trials.

Background: Minimally invasive surgery for intracerebral hemorrhage (ICH) has been evaluated in clinical trials. Although meta-analyses on this topic have been performed in the past, recent trials have added important information to the results of the comparison. However, little work has been done to compare the effect of MIS and conventional treatment on patient prognosis, especially mortality. Methods: PubMed, EMBASE, Web of Science, Ovid, China National Knowledge Infrastructure, and ClinicalTrials.gov were searched on May 1, 2021, for randomized controlled trials of MIS for spontaneous ICH. The primary outcome was defined as death at follow-up, while the secondary outcome was defined as death in different comparisons between MIS and craniotomy (CT) or medication (Me). Results: The initial search yielded 12 high-quality randomized controlled trials involving 2,100 patients. We analyzed the odds ratios (ORs) for MIS compared with conventional treatment, including Me and conventional CT. The OR and confidence intervals (CIs) of the primary and secondary outcomes were 0.62 (0.45-0.85) for MIS vs. conventional treatment. We also conducted subgroup analyses and found that the ORs and CIs for MIS compared with that of conventional treatment in the short-term follow-up were 0.58 (0.42-0.80), and, in the long-term follow-up, was 0.67 (0.46-0.98); and found that ORs were 0.68 (0.48-0.98) for MIS vs. CT and 0.57 (0.41-0.79) for MIS vs. Me. Conclusions: This meta-analysis demonstrates that certain patients with ICH benefit in short- and long-term follow-up from MIS over other treatments, including open surgery and conventional Me. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/.

The Degree of Plasma Oxidized Low-Density Lipoprotein Level Decrease Is Related to Clinical Outcomes for Patients with Acute Ischemic Stroke.

OBJECTIVE: To investigate the relationship between the decrease of plasma oxidized low-density lipoprotein (oxLDL) levels and clinical outcomes in patients with acute atherosclerosis-related ischemic stroke. METHODS: We recruited acute ischemic stroke patients within 3 days of onset consecutively. Plasma oxLDL levels were measured on the second day after admission and before discharge (10-14 days after stroke onset). Initial stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) scores, and infarct volume was measured using diffusion-weighted imaging (DWI) by the ITK-SNAP software. Clinical outcomes were evaluated by DWI volumes in the acute phase, neurological improvement at discharge, and favorable functional prognosis at 90 days. Logistic regression was performed to evaluate the association between oxLDL level decrease and clinical outcomes. RESULTS: 207 patients were enrolled in this study. Compared with the mild decrease of the oxLDL level group, patients with a significant decrease of the oxLDL level group were more likely to have a higher ratio of neurological improvement at discharge (55.07% vs. 14.49%, p < 0.01) and favorable functional prognosis at 90 days (91.30% vs. 55.07%, p < 0.01). In multivariable logistic regression, the degree of oxLDL level decrease was related to neurological improvement at discharge and favorable functional prognosis at 90 days (p < 0.01). Patients with significant decrease were more likely to have neurological improvement at discharge (OR = 7.92, 95% CI, 3.14-19.98, and p < 0.01) and favorable functional prognosis at 90 days (OR = 7.46, 95% CI, 2.40-23.23, and p < 0.01) compared to patients with mild decrease of oxLDL level. The DWI volumes in patients with different oxLDL level decrease groups had no statistical difference (p = 0.41), and the Spearman's rho between oxLDL level decrease and DWI infarct volumes was -0.03, but no statistical difference (p = 0.72). CONCLUSIONS: The degree of oxLDL level decrease is related to neurological improvement at discharge and favorable functional prognosis at 90 days for patients with acute atherosclerosis-related ischemic stroke, but not with infarct volume in the acute phase.

Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Level is Related to Clinical Prognosis In Patients with Acute Atherosclerosis-related Ischemic Stroke.

To investigate the associations between soluble Lectin-like Oxidized Low-density lipoprotein receptor-1 (sLOX-1) and clinical prognosis, especially infarct volume in patients with acute atherosclerosis-related ischemic stroke. We recruited acute ischemic stroke patients within 3 days after onset. Patients were stratified into 3 groups by sLOX-1 level. Initial stroke severity was assessed using the National Institutes of Health Stroke Scale scores, and infarct volume was measured using DWI by ITK-SNAP software. The clinical prognosis was evaluated by DWI volume, clinical response at discharge, and functional outcome at 90 days. Spearman rank correlation analysis was used to examine associations between circulating sLOX-1 levels and infarct volumes. Logistic regression was used to explore the relationship between sLOX-1 levels and clinical prognosis. A total of 207 patients were included in our study. The median DWI volume in the lowest sLOX-1 tertile was 1.98 cm3, smaller than 4.26 cm3 in the highest sLOX-1 group. The Spearman rank correlation coefficient between sLOX-1 levels and DWI volume was 0.47 (P < .01). Compared with the highest sLOX-1 tertiles, patients in the lowest sLOX-1 tertile had a higher risk of favorable functional outcome at 90 days (OR = 3.47, 95% CI, 1.21-9.96) after adjusting traditional risk factors. However, there was no difference between sLOX-1 level and clinical response at discharge. For patients with acute atherosclerosis-related ischemic stroke, circulating sLOX-1 level is correlated with DWI volume in the acute phase and favorable functional outcome at 90 days, but not with the clinical response at discharge.