Background:Dementia with Lewy bodies (DLB) exhibits a more aggressive progression and poorer prognosis than Alzheimer's disease (AD), yet clinical differentiation remains challenging. Dysregulated lipid metabolism, implicated in α-synuclein aggregation and neuroinflammation, may offer specific biomarkers for distinguishing DLB and AD. Methods:This cross-sectional study implemented targeted lipidomic profiling to comprehensively characterize plasma lipidomes in a cohort comprising 50 DLB patients and 56 AD patients. Five machine learning algorithms - least absolute shrinkage and selection operator (LASSO) regression, support vector machine (SVM), random forest (RF), recursive feature elimination (RFE), and stepwise regression - were systematically applied for biomarker discovery. Results:Significant alterations were observed in 7 lipid classes and 65 specific lipid species in DLB compared to AD. DLB plasma exhibited marked elevations in sphingolipids (total Cer, Hex1Cer, SM), lysophospholipids (LPC, LPE), phosphatidic acid (PA), alongside significant reductions in 45 triacylglycerol (TG) species compared to AD. Five machine learning algorithms consistently identified PA(16:0_16:0) and PA(16:0_20:4) as core discriminators between DLB and AD. The LASSO regression model demonstrated superior generalizability in the test set (AUC=0.916), selecting a 11-lipid panel dominated by PA species, alongside PC(18:0_20:4), ChE(22:4), Hex2Cer(d18:1_22:0), and PE species. Conclusion:This first comprehensive targeted lipidomics study reveals distinct plasma lipid signatures differentiating DLB from AD, characterized by upregulated sphingolipids, lysophospholipids, and PA, and downregulated TG. Machine learning identified a 11-lipid biomarker panel, highlighting profound disturbances in glycerophospholipid metabolism. These findings provide novel molecular insights into DLB pathogenesis and a promising diagnostic tool for diagnosis.
INTRODUCTION:Early diagnosis of Post-Stroke Depression (PSD) is challenging. This study aimed to identify possible biomarkers in gut microbiota and plasma metabolites within 72 hours after Acute Ischemic Stroke (AIS) to predict PSD occurring 2 weeks later. METHOD:In this study, 86 patients with AIS were observed within 3 days of stroke onset and followed up for 2 weeks. We collected the feces and plasma within 72 hours of AIS onset for 16S rRNA sequencing and liquid chromatography-mass spectrometry analysis, respectively. RESULTS:At the genus level, PSD patients at 2 weeks following a stroke had a higher relative abundance of Blautia, Eubacterium_hallii_group, Tyzzerella, and a lower abundance of Ellin6067, Massilia, Luedemannella, and Gemmataceae_others within 3 days of AIS onset. Meanwhile, when all metabolites in plasma collected within 72 hours after AIS onset were used to predict 2-week PSD, 31 altered metabolites were identified, of which 28 metabolites increased and 3 decreased, belonging predominantly to steroid and steroid derivatives, glycerophospholipids, fatty acyls, and prenol lipids. The Area Under the Curve (AUC) values for the clinical data, metabolic profiles, gut microbiota, and combined dataset were 0.664 (0.549,0.779), 0.739 (0.621, 0.857), 0.870 (0.781,0.960), and 0.955 (0.888,1), respectively. DISCUSSION:Our study identified potential biomarkers from clinical data, gut bacteria, and plasma metabolites that contribute to PSD. Within 72 hours after AIS, combining these biomarkers from all three sources showed preliminary ability to predict PSD at 2 weeks. Metabolites had the highest contribution, followed by gut bacteria and clinical data. CONCLUSION:A biomarker panel including metabolites, gut microbiota, and clinical data within 72 hours after AIS onset could preliminarily predict PSD 2 weeks later.
Although inflammation and oxidative stress have been increasingly recognised as components of Alzheimer's disease (AD) and Parkinson's disease (PD) pathologies. Few studies have investigated peripheral inflammation, and none have examined oxidative stress in Dementia with Lewy bodies (DLB). The purpose of our study was to characterize and compare those biomarkers in DLB with those in AD and amnestic mild cognitive impairment (aMCI). Plasma samples were obtained from Chinese patients with DLB (n = 50), AD (n = 59), and aMCI (n = 30), and healthy controls (HCs) (n = 54). Peripheral inflammatory biomarkers, including interferon-gamma (IFN-γ), interleukins (IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). Oxidative stress markers, such as superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px), were also assessed. The findings revealed that DLB patients had higher IL-6 levels than AD and HCs and elevated IL-10 and IL-17A levels compared to HCs. In terms of oxidative stress, the levels of SOD were significantly lower and MDA were significantly higher in the DLB and AD compared with HCs. Significant positive correlations were found between Unified Parkinson's Disease Rating Scale (UPDRS) scores and CRP levels. Our study identifies a unique peripheral immune and oxidative stress profile in DLB, characterized by elevated IL-6, MDA, and reduced SOD levels, distinguishing it from AD. These findings, linked to α-synuclein (α-Syn) pathology, provide novel insights into DLB mechanisms and highlight potential biomarkers for disease monitoring, targeted therapies, and future clinical trials.
OBJECTIVE:The National Institutes of Health Stroke Scale (NIHSS) is a known risk factor for post-stroke depression (PSD). However, more objective indicators are needed. The role of neuron-specific enolase (NSE) in PSD development remains unclear. This study aimed to ascertain the correlation of NIHSS score and NSE with PSD risk, and establish a novel nomogram combining NSE and NIHSS for early PSD prediction. METHODS:A total of 172 patients with acute ischemic stroke (AIS) were involved. Baseline clinical data including NSE and NIHSS were collected. At 3-month follow-up, patients were categorized into PSD and non-PSD groups. Logistic models and restricted cubic spline curve were used to investigate the correlation between NIHSS, NSE and PSD. A corresponding nomogram was formulated. RESULTS:Among 172 patients with AIS, 63 (36.63%) were diagnosed with PSD, while 109 (63.37%) were non-PSD. The baseline NIHSS and NSE were positively correlated with the risk of 3-month PSD (P < 0.05). Multivariate logistic regression revealed that sex (OR= 2.168, 95% CI 1.038 ∼ 4.526), age (OR= 1.035, 95% CI 1.002 ∼ 1.070), NIHSS (OR= 1.164, 95% CI 1.022 ∼ 1.325) and NSE (OR= 1.180, 95% CI 1.037 ∼ 1.343) were independently associated with 3-month PSD (all P < 0.05). The nomogram constructed using sex, age, baseline NIHSS score and NSE showed good discrimination, calibration, and clinical utility. CONCLUSION:NSE is a valuable tool for early identification of PSD risk. A combined prediction model incorporating NIHSS and NSE has been established for the personalized prevention and intervention of PSD.
Purpose:The changes in gut microbiota and plasma metabolites have been proposed to play a key role in post stroke depression (PSD), but clinical study based on combined omics is still in lack. This study aimed to investigate the characteristics of gut microbiota and plasma metabolites in patients 3 months after the onset of acute ischemic stroke (AIS), compare PSD and non-PSD groups, and explore possible diagnostic biomarkers. Patients and Methods:Seventy patients with stroke were included at 3 months after AIS onset. Plasma and fecal samples were collected. Gut microbiome was examined using 16S rRNA sequencing, and plasma metabolites were assessed via targeted liquid chromatography-mass spectrometry. Results:Of the 70 patients with ischemic stroke, 25 (35.71%) were diagnosed with PSD. At the genus level, patients with PSD had increased abundance of Parabacteroides, Pyramidobacter, Anaeroglobus, Haliangium, Staphylococcus, CAG-56, Shuttleworthia, and Epulopiscium, and decreased levels of the Eubacterium eligens group and Prevotella. In patients with PSD, 12 plasma metabolites were altered, with cortisol and pyroglutamic acid levels increased, while 2-phosphoglyceric acid, 3-phosphoglycerate, phosphorylcholine, tryptophan, caffeine, N-methylalanine, ornithine, serotonin, theophylline, and vanillic acid were decreased. Enriched metabolic pathways included glutathione, tryptophan, and caffeine metabolism. Furthermore, significant correlations were observed between gut microbial dysregulation and major plasma metabolite alterations. The areas under the curve values of gut microbiota, plasma metabolites, and the combined dataset for PSD diagnosis were 0.704, 0.875, and 0.940, respectively. Conclusion:This study identified the characteristics of gut microbiota and plasma metabolites as well as a panel of combined biomarkers in 3-month PSD, possibly providing a new theoretical framework for diagnosis and treatment.
AIMS:This study aimed to investigate the impact of the triglyceride-glucose index (TyG index) on clinical consequences in individuals with large vascular occlusion (LVO)-induced acute ischemic stroke (AIS) following endovascular treatment (EVT). METHODS:We conducted a single-center retrospective cohort study, including AIS with LVO who underwent EVT. Patients were categorized into TyG index groups, calculated as "(fasting triglyceride [mg/dL] × fasting blood glucose [mg/dL]/2)." Clinical outcomes were assessed, including poor outcome (modified Rankin Scale [mRS] > 2 [3-6]) at 90 days, early neurological deterioration (END), symptomatic intracranial hemorrhage (sICH), and 90-day mortality after EVT. Logistic regression and restricted cubic splines (RCS) were used to examine the relationship between the TyG index and clinical outcomes. Receiver operating characteristic (ROC) curve was constructed to evaluate the prognostic capacity of the TyG index. RESULTS:A total of 424 patients were included. Higher TyG levels were associated with worse functional outcome at 90 days (per unit: p = 0.006), sICH (per unit: p = 0.002, T3 versus T1: p = 0.004), and 90-day mortality (T2 versus T1: p = 0.011, T3 versus T1: p = 0.029) in logistic regression. A RCS model revealed a linear association between the TyG index and poor outcome at 90 days, sICH, and 90-day mortality (p for nonlinearity > 0.05). In ROC curve analysis, the traditional risk factors model (area under the curve [AUC]: 0.824, 95% CI: 0.784-0.859) was outperformed by the conventional risk factors + TyG index model (AUC: 0.845, 95% CI: 0.807-0.878) in predicting poor outcome (p = 0.021). CONCLUSION:A higher TyG index is associated with worse clinical outcomes in LVO-induced AIS patients after EVT. Additionally, the TyG index enhances risk prediction of traditional risk factors for poor outcome.
Backgrounds: Chronic inflammation and oxidative stress play an important role in the pathogenesis of PSD. The main purposes of this study were to examine the dynamic changes of cytokines networks in PSD and the predictive role of early inflammation and oxidative stress for 2-week PSD.Methods: Patients with ischemic stroke were recruited on day 3, and those with Hamilton Depression Rating Scale 24-Item (HAMD-24) >= 8 were classified as ischemic stroke patients with depressive symptoms and others as ischemic stroke patients without depressive symptoms. Subjects were then followed up at 2 weeks and 3 months, with those meeting diagnostic criteria for depressive symptoms on the HAMD >= 8 and the Statistical Manual of Mental Disorders-V (DSM-V) as the PSD group, and the others as the non-PSD group.Results: At 3 days, IFN-gamma, IL-12(p70), IL-12(p40), IL-2, IL-28A/IFN lambda 2, and IL-19 were elevated in ischemic stroke patients with depressive symptoms. At 2 weeks, IL-12(p40), IL-19, IL-22, IFN-beta and MMP-1 all were increased in PSD patients. At 3 months, IL-2, IFN-beta and sCD163 increased in PSD group. Longitudinally, the inflammatory response decreased significantly in PSD group from 2 weeks to 3 months of follow-up, while it gradually decreased in non-PSD group from 3 days to 3 months of follow-up. SOD was positively related to IL-12(p70), IFN-gamma and IL-20. Plasma IFN-gamma at 3 days may be a potential predictive biomarker for 2-week PSD.Conclusions: Peripheral inflammation and oxidative stress are involved in the pathogenesis of PSD, providing new insights for its diagnosis and treatment.
Lipid metabolism and oxidative stress are key mechanisms in Alzheimer's disease (AD). The link between plasma lipid metabolites and oxidative stress in AD patients is poorly understood. This study was to identify markers that distinguish AD and amnestic mild cognitive impairment (aMCI) from NC, and to reveal potential links between lipid metabolites and oxidative stress. We performed non-targeted lipid metabolism analysis of plasma from patients with AD, aMCI, and NC using LC–MS/MS. The plasma malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) levels were assessed. We found significant differences in lipid metabolism between patients with AD and aMCI compared to those in NC. AD severity is associated with lipid metabolites, especially TG (18:0_16:0_18:0) + NH4, TG (18:0_16:0_16:0) + NH4, LPC(16:1e)-CH3, and PE (20:0_20:4)-H. SPH (d16:0) + H, SPH (d18:1) + H, and SPH (d18:0) + H were high-performance markers to distinguish AD and aMCI from NC. The AUC of three SPHs combined to predict AD was 0.990, with specificity and sensitivity as 0.949 and 1, respectively; the AUC of three SPHs combined to predict aMCI was 0.934, with specificity and sensitivity as 0.900, 0.981, respectively. Plasma MDA concentrations were higher in the AD group than in the NC group ( p = 0.003), whereas plasma SOD levels were lower in the AD ( p < 0.001) and aMCI ( p = 0.045) groups than in NC, and GSH-Px activity were higher in the AD group than in the aMCI group ( p = 0.007). In addition, lipid metabolites and oxidative stress are widely associated. In conclusion, this study distinguished serum lipid metabolism in AD, aMCI, and NC subjects, highlighting that the three SPHs can distinguish AD and aMCI from NC. Additionally, AD patients showed elevated oxidative stress, and there are complex interactions between lipid metabolites and oxidative stress.
Dementia with Lewy Bodies (DLB) is a complex neurodegenerative disorder that often overlaps clinically with Alzheimer’s disease (AD), presenting challenges in accurate diagnosis and underscoring the need for novel biomarkers. Lipidomic emerges as a promising avenue for uncovering disease-specific metabolic alterations and potential biomarkers, particularly as the lipidomics landscape of DLB has not been previously explored. We aim to identify potential diagnostic biomarkers and elucidate the disease's pathophysiological mechanisms. This study conducted a lipidomic analysis of plasma samples from patients with DLB, AD, and healthy controls (HCs) at Xuanwu Hospital. Untargeted plasma lipidomic profiling was conducted via liquid chromatography coupled with mass spectrometry. Machine learning methods were employed to discern lipidomic signatures specific to DLB and to differentiate it from AD. The study enrolled 159 participants, including 57 with AD, 48 with DLB, and 54 HCs. Significant differences in lipid profiles were observed between the DLB and HC groups, particularly in the classes of sphingolipids and phospholipids. A total of 55 differentially expressed lipid species were identified between DLB and HCs, and 17 between DLB and AD. Correlations were observed linking these lipidomic profiles to clinical parameters like Unified Parkinson’s Disease Rating Scale III (UPDRS III) and cognitive scores. Machine learning models demonstrated to be highly effective in distinguishing DLB from both HCs and AD, achieving substantial accuracy through the utilization of specific lipidomic signatures. These include PC(15:0_18:2), PC(15:0_20:5), and SPH(d16:0) for differentiation between DLB and HCs; and a panel includes 13 lipid molecules: four PCs, two PEs, three SPHs, two Cers, and two Hex1Cers for distinguishing DLB from AD. This study presents a novel and comprehensive lipidomic profile of DLB, distinguishing it from AD and HCs. Predominantly, sphingolipids (e.g., ceramides and SPHs) and phospholipids (e.g., PE and PC) were the most dysregulated lipids in relation to DLB patients. The lipidomics panels identified through machine learning may serve as effective plasma biomarkers for diagnosing DLB and differentiating it from AD dementia.
目的 探讨术前炎性反应相关指标对急性大血管闭塞性卒中患者血管内治疗(EVT)术后90d临床预后的影响.方法 回顾性连续纳入2019 年1 月至2021 年1 月在首都医科大学宣武医院急诊科和神经内科接受EVT的急性大血管闭塞性卒中患者,根据术后 90d改良Rankin量表(mRS)评分结果,将其分为预后良好组与预后不良组.以mRS评分 0~2 分为预后良好,3~6 分为预后不良,其中6 分为死亡.收集并分析两组患者的基线资料、血管危险因素、术前实验室检测指标、术前炎性反应相关指标[中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)、全身炎症反应指数(SIRI)和系统性免疫炎症指数(SII)]、就诊流程时间、脑梗死分型及血管病变部位等临床资料.将单因素分析中P<0.05 且临床意义较大的项目为自变量纳入多因素Logistic回归分析,探讨EVT术后 90d预后不良的独立影响因素.结果 共纳入 426 例患者,其中预后良好组152 例(35.7%),预后不良组274 例(64.3%).(1)与预后良好组相比,预后不良组患者年龄、入院收缩压、入院美国国立卫生研究院卒中量表(NIHSS)评分、术后 NIHSS评分均较高[67(58,76)岁比 62(54,70)岁,Z =-4.293;153(138,170)mmHg比143(130,160)mmHg,Z =-3.559;17(13,21)分比14(11,18)分,Z =-4.550;17(11,21)分比9(5,14)分,Z =-7.558],男性、饮酒比例均较低[60.2%(165/274)比 77.0%(117/152),χ2 =12.265;23.4%(64/274)比37.5%(57/152),χ2 =9.615],糖尿病、卒中、冠心病比例均较高[33.6%(92/274)比19.7%(30/152),χ2 =9.163;34.3%(94/274)比 20.4%(31/152),χ2 =9.126;28.1%(77/274)比 17.1%(26/152),χ2 =6.449],入院Alberta卒中项目早期CT评分(ASPECTS)较低[8(7,9)分比 9(8,10)分,Z =-9.134],组间差异均有统计学意义(均P<0.05).两组体质量指数、高血压病、高脂血症、心房颤动、吸烟、入院舒张压的差异均无统计学意义(均P>0.05).(2)与预后良好组相比,预后不良组患者急诊快测血糖、空腹血糖、中性粒细胞计数、C反应蛋白、D-二聚体、NLR、PLR、SIRI及SII水平均较高,淋巴细胞计数和单核细胞计数均较低,组间差异均有统计学意义[7.5(6.3,9.8)mmol/L比6.9(6.0,8.4)mmol/L,Z =-2.904;7.5(6.2,10.6)mmol/L比6.5(5.3,8.3)mmol/L,Z =-5.177;7.4(5.1,9.7)×109/L比6.5(5.0,8.6)×109/L,Z=-2.012;29.2(13.0,78.1)mg/L比12.6(7.1,17.7)mg/L,Z=-3.370;1.1(0.5,2.7)mg/L比0.6(0.3,1.7)mg/L,Z =-3.582;6.5(4.0,10.5)比5.1(2.9,7.7),Z=-3.614;185.2(123.1,281.6)比153.8(103.8,217.6),Z =-3.229;2.2(1.3,3.6)比1.7(1.1,3.0),Z =-2.222;1361(758,2401)比 1019(535,1746),Z =-3.265;1.1(0.8,1.6)×109/L比1.4(1.1,1.9)×109/L,Z =-3.513;0.38(0.28,0.48)×109/L比0.41(0.32,0.52)×109/L,Z =-2.334;均P<0.05];白细胞计数的组间差异无统计学意义(P>0.05).(3)与预后良好组相比,预后不良组患者血管再通达改良脑梗死溶栓(mTICI)分级2b~3 级的比例较低,发生症状性颅内出血(sICH)及肺炎比例均较高,组间差异均有统计学意义[85.8%(235/274)比 93.4%(142/152),χ2 =5.627;22.6%(62/274)比 2.6%(4/152),χ2 =29.857;54.4%(149/274)比 28.3%(43/152),χ2 =26.881;均P<0.05];两组急性卒中Org 10172 治疗试验(TOAST)分型、流程时间及闭塞血管部位的差异均无统计学意义(均P>0.05).(4)多因素Logistic回归分析显示,既往卒中(OR =2.302,95%CI:1.350~3.926,P =0.002)、冠心病史(OR =1.902,95%CI:1.072~3.372,P =0.028)、入院收缩压升高(OR =1.016,95%CI:1.006~1.026,P =0.002)、入院 NIHSS评分高(OR =1.048,95%CI:1.014~1.083,P =0.006)、术后并发肺炎(OR =2.330,95%CI:3.657~31.741,P<0.01)、术后并发sICH(OR =10.774,95%CI:1.141~5.897,P<0.01)、mTICI分级<2b级(OR =2.594,95%CI:1.014~1.083,P =0.023)、高NLR(OR =1.135,95%CI:1.056~1.219,P =0.001)是急性大血管闭塞性卒中患者EVT后 90d预后的独立危险因素,高 SIRI是 EVT后 90d预后的保护因素(OR =0.898,95%CI:0.809~0.997,P =0.045).结论 术前高NLR可能增加急性大血管闭塞卒中患者EVT后90d预后不良的风险,术前SIRI水平尚不能用于对EVT后90d预后的评价.本研究结果有待于未来扩大样本量以及行多中心前瞻性EVT的炎性反应指标研究进一步证实.
Background The Dural Arteriovenous Fistulas (DAVFs) secondary to cerebral venous sinus thrombosis (CVST) are rather rare. The aim of present study is to investigate the clinical and radiological features, and treatment outcome of DAVFS in patients following CVST. Methods Data about demographic information, clinical presentations, radiological findings, as well as treatment and outcome of DAVFs sequence to CVST were collected to analysis from January 2013 to September 2020 in this retrospective study. Results Fifteen patients with DAVFs after CVST were included in the study. The median age was 41 years (range17-76 years). Ten patients (66.67%) were male and 6 patients (33.33%) were female. The median duration of presenting CVST was 182 days (Range 20–365). Mean time from diagnosis of CVST to confirmation of DAVFs was 97 days (range 36–370 days). The most common manifestations of DAVFs following CVST were headache and visual disturbance seen in 7 patients respectively. Five patients had pulsatile tinnitus (%) and 2 had nausea/vomiting. The DAVFs are most frequently located at the transverse/sigmoid sinus (7/15, 46.67%), followed by the superior sagittal the sinus and confluence sinus (6/15, 40.00%) respectively. Angiography of DAVFs revealed Board type I in seven (46.7%) patients, Board type II and III in 4(26.7%) patients, respectively. The Cognard I was noted in seven (46.7%), Cognard IIa and IV in 3 patients, IIb and III in one patient, respectively. The main feeding arteries of DAVFs most commonly originate from the branches of the external carotid artery in 6 (40.0%) patients. The other DAVFs are conjointly supplied by multiple feeders from internal and external carotid artery and vertebral arteries. Fourteen (93.33%) patients were treated with endovascular embolization and none of the patients had permanent deficits during follow-up. Conclusion Intracranial DAVFs following CVST are rare presentations. Most patients have a good outcome after timely interventional therapy. Continued observation and follow-up of (DSA) are important to find DAVFs secondary to CVST.
目的 探究糖化血红蛋白(HbA1c)及随机血糖与急性大血管闭塞性缺血性卒中患者血管内治疗临床预后的关系.方法 回顾性连续纳入2019年1月至2020年12月于首都医科大学宣武医院卒中中心接受血管内治疗的急性大血管闭塞卒中患者,收集患者基线资料(年龄和性别)、血管危险因素(包括吸烟、饮酒、高血压病、高脂血症、糖尿病、心房颤动、既往卒中和冠心病)、既往降糖药物使用、入院时血压和随机血糖、术后在院期间空腹HbA1c、入院时美国国立卫生研究院卒中量表(NIHSS)评分、闭塞血管部位、脑梗死分型、血管内治疗后再灌注情况,以及术前实验室检查包括血红蛋白、纤维蛋白原、中性粒细胞与淋巴细胞比值(NLR).根据入院随机血糖7.8 mmol/L和术后在院期间空腹HbA1c 6.5%,将患者分为HbA1c及随机血糖正常组(HbA1c<6.5%且随机血糖<7.8 mmol/L)、HbA1c或随机血糖增高组(HbA1c≥6.5%、随机血糖<7.8 mmol/L或HbA1c<6.5%、随机血糖≥7.8 mmol/L)、HbA1c及随机血糖均高组(HbA1c≥6.5%且随机血糖≥7.8 mmol/L)3组,对3组患者的基本资料和治疗情况进行比较.根据术后90 d改良Rankin量表(mRS)评分将患者分为预后不良和预后良好组,mRS评分0~2分为预后良好,3~6分为预后不良,6分为死亡,并进行单因素分析和二元多因素Logistic回归分析,分析随机血糖和HbA1c对术后90 d神经功能预后的影响.对随机血糖和HbA1c联合指标进行受试者工作特征(ROC)曲线分析,得出其对术后90 d不良预后的预测效能.结果 最终纳入246例患者,其中HbA1c及随机血糖正常组77例,HbA1c或随机血糖增高组97例,HbA1c及随机血糖均高组72例.3组患者年龄、高血压病、糖尿病、既往降糖药物使用、入院随机血糖、术后在院空腹HbA1c、NLR、纤维蛋白原水平差异均有统计学意义(均P<0.05).组间两两比较结果显示,HbA1c及随机血糖均高组患者相较于其他两组高血压病、糖尿病及既往降糖药物使用患者比例均高(均P<0.05),入院随机血糖、术后在院空腹HbA1c及纤维蛋白原水平偏高(均P<0.05);HbA1c及随机血糖均高组患者相较于HbA1c及随机血糖正常组年龄偏大(P=0.018),HbA1c或随机血糖增高组相较于HbA1c及随机血糖正常组入院随机血糖及NLR偏高(均P<0.05).术后90 d预后良好者102例(41.46%),预后不良者144例(58.54%),死亡51例(20.73%).与预后良好组患者相比,预后不良组患者年龄偏大,既往患糖尿病、冠心病比例较高,入院NIHSS评分、入院收缩压、纤维蛋白原水平偏高,改良脑梗死溶栓(mTICI)分级2b~3级比例较低,症状性颅内出血比例较高,HbA1c及随机血糖正常患者比例较低,HbA1c及随机血糖均高患者比例较高(均P<0.05).矫正潜在协变量后,与HbA1c及随机血糖正常组相比,HbA1c及随机血糖均高组术后90 d预后不良风险增加(OR=2.532,95%CI:1.148~5.586,P=0.021).HbA1c联合随机血糖预测术后90 d预后不良的曲线下面积为0.649(95%CI:0.580~0.719,P<0.01).结论 糖化血红蛋白与随机血糖同时增高与急性大血管闭塞性缺血性卒中患者接受血管内治疗后的90 d预后不良相关.
Lipid metabolism and oxidative stress are key mechanisms in Alzheimer's disease (AD). The link between plasma lipid metabolites and oxidative stress in AD patients is poorly understood. This study was to identify markers that distinguish AD and amnestic mild cognitive impairment (aMCI) from NC, and to reveal potential links between lipid metabolites and oxidative stress. We performed non-targeted lipid metabolism analysis of plasma from patients with AD, aMCI, and NC using LC-MS/MS. The plasma malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) levels were assessed. We found significant differences in lipid metabolism between patients with AD and aMCI compared to those in NC. AD severity is associated with lipid metabolites, especially TG (18:0_16:0_18:0) + NH4, TG (18:0_16:0_16:0) + NH4, LPC(16:1e)-CH3, and PE (20:0_20:4)-H. SPH (d16:0) + H, SPH (d18:1) + H, and SPH (d18:0) + H were high-performance markers to distinguish AD and aMCI from NC. The AUC of three SPHs combined to predict AD was 0.990, with specificity and sensitivity as 0.949 and 1, respectively; the AUC of three SPHs combined to predict aMCI was 0.934, with specificity and sensitivity as 0.900, 0.981, respectively. Plasma MDA concentrations were higher in the AD group than in the NC group (p = 0.003), whereas plasma SOD levels were lower in the AD (p < 0.001) and aMCI (p = 0.045) groups than in NC, and GSH-Px activity were higher in the AD group than in the aMCI group (p = 0.007). In addition, lipid metabolites and oxidative stress are widely associated. In conclusion, this study distinguished serum lipid metabolism in AD, aMCI, and NC subjects, highlighting that the three SPHs can distinguish AD and aMCI from NC. Additionally, AD patients showed elevated oxidative stress, and there are complex interactions between lipid metabolites and oxidative stress.
BackgroundSymptomatic intracranial hemorrhage (sICH) is a devastating complication of endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) and is associated with high risk of disability and mortality. This study intended to evaluate the predictors of sICH after EVT in patients with large vessel occlusion (LVO)-induced AIS.MethodsWe conducted a retrospective review on consecutive AIS patients who underwent EVT in our University hospital between January 2019 and August 2020. The patients were classified into two groups based upon the occurrence of sICH. The main outcomes were the occurrence of sICH using the Heidelberg Bleeding Classification and functional condition at 90 days. Multivariate logistic regression analysis and receiver operating characteristics (ROC) curves were used to identify independent predictors of sICH after EVT.ResultsThree hundred and 69 patients were enrolled in the study, of which 16.8% (n = 62) developed sICH. Favorable neurological outcome was lower in patients with sICH than in patients without sICH (6.5 vs. 43.3%; P < 0.001), with the overall mortality being 112 (30.4%) at 90 days post- EVT. Results from univariate analysis showed significant differences between the two groups in the prevalence of diabetes, initial Alberta Stroke Program Early CT Score (ASPECTS) score, National Institutes of Health Stroke Scale (NIHSS) score after operation, the levels of fasting blood glucose (FBG), neutrophil to lymphocyte ratio (NLR), platelets (PLT), and thrombin time (TT) at admission. Multivariate logistic regression analysis showed that FBG ≥ 7.54 mmol/L (OR: 2.765; 95% confidence interval [CI]: 1.513–5.054), NLR ≥ 5.48 (OR: 2.711; 95% CI: 1.433–5.128), TT at admission ≥ 16.25 s (OR: 2.022; 95% CI: 1.115–3.667), and NIHSS score within 24 h after the operation ≥ 10 (OR: 3.728; 95% CI: 1.516–9.170) were independent predictors of sICH. The combination of NLR ≥ 5.48, FBG ≥ 7.54 mmol/L, TT at admission ≥ 16.25 s, and NIHSS score within 24 h after the operation ≥ 10 generated an optimal prediction model (AUC: 0.723).ConclusionHigher levels of FDG, NLR, TT at admission, and NIHSS score after operation were associated with sICH after EVT in patients with LVO-induced AIS.
目的 探讨血管内治疗的急性大血管闭塞性缺血性卒中患者入院血压与术后90d神经功能预后之间的关系.方法 回顾性分析2018年1月至2019年12月于首都医科大学宣武医院神经内科接受血管内治疗的急性大血管闭塞性卒中患者的基线资料[包括年龄、性别、体质量指数、血管危险因素、入院时即刻血压情况、卒中前改良Rankin量表(mRS)评分、美国国立卫生研究院卒中量表(NIHSS)评分、Alberta卒中项目早期CT评分、实验室检查结果及梗死部位(前循环、后循环)]以及血管内治疗相关信息(发病至治疗时间和闭塞血管再通程度)以及术后90 d神经功能预后、术后症状性颅内出血等.入院时记录基线收缩压和舒张压.闭塞血管再通评估采用改良脑梗死溶栓(mTICI)分级,术后90 d神经功能预后以mRS评估(mRS评分0~2分为预后良好,>2分为预后不良,其中6分为死亡),将所有患者依据术后90 d预后情况分为预后良好组与预后不良组.采用Spearman相关性分析方法评价入院血压与术后90 d mRS评分的关系,采用Logistic回归分析方法分析术后90 d时预后不良的影响因素.采用受试者工作特征(ROC)曲线评价入院血压对术后90 d预后不良的预测价值,依据截断值,将所有患者分成较高血压组(入院收缩压高于截断值)与较低血压组(入院收缩压低于截断值),分析不同收缩压患者的术后90 d mRS评分、良好预后比例及死亡情况.结果 共入组369例患者,血管内治疗后血管再通322例(87.3%);术后症状性颅内出血62例(16.8%);术后90 d,137例(37.1%)患者预后良好,232例(62.9%)患者预后不良.入院收缩压与术后90 d神经功能预后相关(r=0.212,P<0.01).预后不良组患者入院收缩压高于预后良好组[155(139,170)mmHg比142(130,162)mmHg,Z=-3.559,P<0.01].Logistic回归分析结果显示,入院收缩压(OR=1.016,95%CI:1.005~1.028,P=0.004)、高脂血症病史(OR=0.550,95%CI:0.310~0.977,P=0.042)、卒中病史(OR=2.016,95%CI:1.125~3.613,P=0.019)、入院NIHSS评分(OR=1.063,95%CI:1.026~1.101,P=0.001)、血管再通(OR=0.387,95%CI:0.168~0.892,P=0.026)、术后症状性颅内出血(OR=11.690,95%CI:3.890~35.131,P<0.01)为急性大血管闭塞性卒中患者血管内治疗后90 d神经功能预后的独立影响因素.入院收缩压作为神经功能预后预测因子的曲线下面积为0.611(95%CI:0.552~0.669,P<0.01),入院收缩压149.5 mmHg是预测预后的最佳截断值.与入院收缩压≥149.5 mmHg(较高血压组,206例)患者比较,入院收缩压<149.5 mmHg(较低血压组,163例)患者的术后90 d mRS评分较低[中位数评分:3(1,5)分比4(2,6)分,Z=-4.022,P<0.01),术后90 d预后良好比例较高[47.9%(78/163)比28.6%(59/206),χ2=14.389,P<0.01],术后90 d病死率较低[23.3%(38/163)比35.9%(74/206),χ2=6.844,P=0.009].结论 对于接受血管内治疗的急性大血管闭塞性卒中患者,较高的入院收缩压是术后90 d不良神经功能预后的独立预测因子.
1Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Ophthalmology, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Department of Emergency, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China Background and Objective: Essential thrombocythemia (ET) is a rare cause of cerebral venous sinus thrombosis (CVST). Analysis of the risk factors and treatment therapies of CVST in ET has yielded controversial findings. Subjects and Methods: We retrospectively investigated the clinical characteristics of CVST events in ET and compared baseline characteristics, causative factors, hematological effects, and treatments between ET patients with and without CVST. Results: Overall, 91 of 115 patients who met the ET diagnosis were included in this study. Among them, 23 (25.27%) patients met the diagnostic criteria of ET with CVST for inclusion, 14 (60.87%) of whom were females, with a median age of 34 (range 25–50). CVST diagnosis was made concomitantly to ET in 19 patients (82.61%). The most common symptom and sites of thrombosis of CVST was an acute or subacute headache and sigmoid sinuses, respectively. Compared with ET patients without CVST, ET patients with CVST were significantly younger (37.65±14.45 vs 60.93±13.46, P<0.001) and had lower prevalence of hypertension (4.34 vs 32.35%, P=0.003) and coronary artery disease (0 vs 14.71%, P = 0.045). Patients with CVST presented with significant lower platelet count (510.39±176.71 vs 750.82±249.10, P< 0.001) and higher score of IPSET-thrombosis (P=0.017). Multivariate logistic regression analysis indicated that age (P=0.002, OR 1.096, 95% CI 1.035–1.161), at least one CVRF (P = 0.024, OR 0.037, 95% CI 0.002–0.649), platelet count (P=0.045, OR 0.994, 95% CI 0.989–1.001), and lower percentage of antiplatelet therapy (P=0.035, OR 0.307, 95% CI 0.001-1.280) significantly contributed to the risk of CVST in ET. Conclusion: Most patients (95.65%) had a favorable outcome without recurrence after standard anticoagulant and cytoreductive treatment at last follow-up. These findings indicate that CVST may be the initial presentation of ET, with its detection crucial for early diagnosis and appropriate management. Anticoagulant and cytoreductive therapies should be recommended for preventing ET-related CVST with JAK2 V617F mutation.
OBJECTIVE The investigators aimed to explore the clinical characteristics, immunotherapy, and outcomes of patients with antileucine-rich glioma-inactivated-1 (anti-LGI1) encephalitis. METHODS Data on participants' clinical characteristics, laboratory findings, radiological and electroencephalogram (EEG) features, treatment, and outcomes from January 2012 to December 2016 were collected. Statistical analysis was conducted to assess the factors associated with patient functional outcome. Forty-three patients were enrolled in the study, with a predominance of males (65.1%). The median age at onset was 57 years (interquartile range [IQR]: 44.0-65.0). The median time from onset to diagnosis was 60 days (IQR: 37.0-127.0). RESULTS The main clinical manifestations included epilepsy (100%), faciobrachial dystonic seizures (FBDS; 44.2%), cognitive dysfunction (95.3%), neuropsychiatric disturbances (76.7%), sleep disorders (58.1%), and disturbance of consciousness (48.8%). Twenty-two patients (51.2%) had hyponatremia, 31 (72.1%) had abnormal EEG results, and 30 (69.8%) had abnormal brain MRI scans, mainly involving the hippocampus (76.7%) or temporal lobe (40%). Twenty of 34 patients (58.8%) in a follow-up MRI examination exhibited hippocampal atrophy. Twenty-five patients (58.2%) were administered corticosteroids and intravenous immunoglobulin, whereas 17 patients were treated only with corticosteroids. Forty-one patients (95.3%) had favorable outcomes after a median of 21.5 months (IQR: 7-43) of follow-up. Serum sodium level was a factor associated with a disabled status (odds ratio=0.81, 95% CI=0.66, 0.98, p=0.03). Anti-LGI1 encephalitis patients were characterized by seizures, FBDS, cognitive deficits, neuropsychiatric disturbances, and hyponatremia. CONCLUSIONS Most patients with anti-LGI1 encephalitis are nonparaneoplastic, have low recurrence rates, and have favorable prognostic outcomes. Rapid evaluation, prompt immunotherapy, and long-term follow-up are essential in the care of anti-LGI1 encephalitis patients.
目的 分析延-颈交界区硬脊膜动静脉瘘(Spinal dural arteriovenous fistulas,SDAVF)的临床、影像学特点,以提高临床医生对延-颈交界区SDAVF的认识和诊断水平.方法 回顾性分析7例表现为脑干充血的硬脊膜动静脉瘘患者的临床特点、影像学资料.结果 7例患者均为男性,平均年龄57.4岁;急性起病4例,慢性进展性2例;主要症状包括肢体无力(5例)、头晕(3例)、行走不稳(1例)、感觉障碍(3例)、构音障碍(1例)、顽固性呃逆(1例)、呼吸困难(1例)、颈部疼痛(1例)、大小便障碍(1例);核磁共振成像(Magnetic resonance imaging,M RI)显示脑干受累部位主要在延髓,可见延髓增粗和髓内异常信号灶,脊髓周围有迂曲、虫蚀样血管流空影;数字减影血管造影(Digital subtract angiography,DSA)显示脊髓引流静脉迂曲扩张,向上(4例)或向下(3例)引流,瘘口位于颅-颈交界区水平;所有患者接受手术治疗后症状改善.结论 颅-颈交界区SDAVF可表现为脑干功能障碍,临床表现无特异性,易误诊;MRI可作为初步诊断方法,选择性脊髓血管造影是确诊的金标准;及早治疗可逆转神经功能障碍.
Background and Objective Essential thrombocythemia (ET) is a rare cause of cerebral venous sinus thrombosis (CVST). Analysis of the risk factors and treatment therapies of CVST in ET has yielded controversial findings. Subjects and Methods We retrospectively investigated the clinical characteristics of CVST events in ET and compared baseline characteristics, causative factors, hematological effects, and treatments between ET patients with and without CVST. Results Overall, 91 of 115 patients who met the ET diagnosis were included in this study. Among them, 23 (25.27%) patients met the diagnostic criteria of ET with CVST for inclusion, 14 (60.87%) of whom were females, with a median age of 34 (range 25–50). CVST diagnosis was made concomitantly to ET in 19 patients (82.61%). The most common symptom and sites of thrombosis of CVST was an acute or subacute headache and sigmoid sinuses, respectively. Compared with ET patients without CVST, ET patients with CVST were significantly younger (37.65±14.45 vs 60.93±13.46, P<0.001) and had lower prevalence of hypertension (4.34 vs 32.35%, P=0.003) and coronary artery disease (0 vs 14.71%, P = 0.045). Patients with CVST presented with significant lower platelet count (510.39±176.71 vs 750.82±249.10, P< 0.001) and higher score of IPSET-thrombosis (P=0.017). Multivariate logistic regression analysis indicated that age (P=0.002, OR 1.096, 95% CI 1.035–1.161), at least one CVRF (P = 0.024, OR 0.037, 95% CI 0.002–0.649), platelet count (P=0.045, OR 0.994, 95% CI 0.989–1.001), and lower percentage of antiplatelet therapy (P=0.035, OR 0.307, 95% CI 0.001-1.280) significantly contributed to the risk of CVST in ET. Conclusion Most patients (95.65%) had a favorable outcome without recurrence after standard anticoagulant and cytoreductive treatment at last follow-up. These findings indicate that CVST may be the initial presentation of ET, with its detection crucial for early diagnosis and appropriate management. Anticoagulant and cytoreductive therapies should be recommended for preventing ET-related CVST with JAK2 V617F mutation.
Antiphospholipid syndrome (APS) with cerebral venous sinus thrombosis (CVST) is a relatively rare phenomenon, and this observational study aimed to investigate the clinical characteristics of APS patients complicated with CVST. We retrospectively investigated the clinical characteristics of CVST events in APS and compared differential characteristics and associated factors between APS patients with and without CVST. Twenty-one CVST patients with APS were enrolled including 14 females (9.4%) and 7 males (5.8%). The median age and disease duration at onset of CVST was 33 years (IQR 28-48) old and 1.3 months (IQR 0.7-4), respectively. Among APS patients with CVST, 12 (57.1%) cases presented with neurologic symptoms of CVST as the initial manifestation. Onset of CVST was mainly chronic (52.4%). Headache (90.5%) was the most common neurological symptom. The common locations of CVST were transverse sinus (76.2%) and superior sagittal sinus (57.1%), with more frequently (76.2%) dual or multiple sinuses involved. All patients with CVST were treated with anticoagulant, and 5 (23.8%) patients received endovascular therapy. Sixteen (84.2%) patients had good outcomes and 3 (15.8%) patients died at last follow-up. There were no significant differences (P > 0.05) between two groups in the analysis of related APS indicators. There were no significant differences (P > 0.05) between two groups in the analysis of related APS indicators. Although APS complicated with CVST is rare and predominately chronic developed. The evaluation of CVST should be performed for APS patients with intracranial hypertension syndrome. The routine screening of antiphospholipid antibodies (aPLs) is highly recommended in unexplained CVST patients. Most CVST patients with APS will have a good prognosis after treatment, and endovascular therapy is an alternative treatment.