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BACKGROUND AND PURPOSE: Preclinical studies have shown that metformin has neuroprotective actions in stroke. However, the optimal treatment timing and duration remain unknown. Herein, we examined the efficacy of metformin treatment on prognosis in acute ischemic stroke (AIS) patients, and assessed the optimal treatment timing and duration. METHODS: AIS patients with type 2 diabetes mellitus were retrospectively enrolled. Patients were grouped into those who never received metformin (MET - group), those who received metformin continuously before stroke and after admission (pre-stroke + /post-stroke + group), those who only received metformin before stroke onset (pre-stroke + /post-stroke - group), and those who only received metformin after admission (pre-stroke - /post-stroke + group). The all MET + group represents the sum of the three metformin treatment groups. The efficacy outcome was the 90-day modified Rankin Scale (mRS) score. RESULTS: In total, 309 eligible patients were included (MET - [N = 130], pre-stroke + /post-stroke + [N = 94], pre-stroke + /post-stroke - [N = 30], pre-stroke - /post-stroke + [N = 55]; all MET + [N = 179]). The all MET + group had a trend toward a lower 90-day mRS score compared with that in the MET - group (1 [0-2] vs 1 [0-3], unadjusted odds ratio [OR] = 0.652, P = 0.041; adjusted OR = 0.752, P = 0.218). In the three metformin treatment groups, only the pre-stroke + /post-stroke + group had a significantly lower 90-day mRS score (1 [0-1] vs 1 [0-3], adjusted OR = 0.497, 95%CI = 0.289-0.854; P = 0.011) and higher proportion of mRS score 0-1 (78.7% vs. 61.5%, adjusted OR = 2.278, 95%CI = 1.108-4.680; P = 0.025) than the MET - group. CONCLUSION: AIS patients with type 2 diabetes mellitus who receive continuous metformin treatment before stroke onset and after admission have improved functional outcome at 90 days.
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Isquemia Encefálica , Diabetes Mellitus Tipo 2 , AVC Isquêmico , Metformina , Acidente Vascular Cerebral , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/uso terapêutico , Estudos Retrospectivos , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Acidente Vascular Cerebral/terapia , Resultado do TratamentoRESUMO
OBJECTIVES: Elevated platelet distribution width (PDW) is a recognized marker of platelet activity. Herein, we investigated the association between admission PDW values and clinical outcome at 3 months in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy (MT). MATERIALS AND METHODS: We retrospectively collected consecutive patients diagnosed with AIS following MT from two stroke centers. PDW was measured on admission. Subjects were divided into two groups according to the clinical outcome using the modified Rankin Scale at 3 months. Multiple regression analyses and receiver operating characteristic (ROC) curves were performed to determine the associations between admission PDW values, clinical parameters, and functional outcome. RESULTS: A total of 162 subjects were enrolled. Patients in the poor outcome group had a significantly higher percentage of PDW >16.0 fL compared with the good outcome group (57.3% vs. 26.9%, P < 0.001). After adjusting for a range of confounding factors, multiple regression analysis showed that PDW >16.0 fL was an independent predictor of poor outcome at 3 months (odds ratio 4.572, 95% confidence interval 1.896-11.026, P = 0.001). ROC curve analysis revealed that PDW >16.0 fL predicted poor outcome with 57.3% sensitivity and 73.1% specificity (the area under the ROC curve 0.637, 95% confidence interval 0.558-0.711, P = 0.004). CONCLUSIONS: Elevated PDW is an independent predictor of poor functional outcome in patients with anterior circulation AIS undergoing MT at 3 months.
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AVC Isquêmico , Volume Plaquetário Médio , Trombólise Mecânica , Humanos , AVC Isquêmico/sangue , AVC Isquêmico/terapia , Trombólise Mecânica/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Following acute ischemic stroke (AIS), approximately half of patients do not achieve recanalization after intravenous administration of tissue plasminogen activator (rt-PA). Thrombolysis resistance is a possible reason for recanalization failure. Thrombolysis resistance is likely related to the ultrastructure and composition of the thrombus. However, there is a paucity of published information on the relationship between thrombus ultrastructure and thrombolysis resistance. CASE PRESENTATION: Two patients who underwent mechanical thrombectomy were observed within 4.5 h after stroke onset. One patient failed to respond to rt-PA (defined as thrombolysis resistant), and the other patient did not receive rt-PA treatment (non-rtPA). In each patient, the occluded artery was the internal carotid artery or middle cerebral artery. According to the Trial of ORG 10172 in Acute Stroke Treatment classification, both patients had large atherosclerotic cerebral infarction. By scanning electron microscopy (SEM) and transmission electron microscopy (TEM), we found that the thrombus structure was significantly different between the two patients. CONCLUSION: Grid-like dense fibrin, compressed polyhedral erythrocytes, and large accumulation of neutrophils may be characteristics of thrombolysis resistant thrombi.
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Isquemia Encefálica/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Trombose/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Artéria Carótida Interna/patologia , Feminino , Humanos , Masculino , Artéria Cerebral Média/patologia , Terapia Trombolítica/métodos , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: The role of bilirubin in patients treated with mechanical thrombectomy (MT) is unknown. We investigated the relationship between admission bilirubin levels and hemorrhagic complication in acute ischemic stroke (AIS) patients treated with MT and detailed the roles of direct bilirubin (DB), indirect bilirubin (IDB), and total bilirubin (TB). METHODS: Consecutive AIS patients treated with MT were enrolled from two stroke centers. Outcome measures included hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) within 48 h. An independent association of bilirubin with outcomes was identified by multivariate logistic regression analysis. The accuracies of bilirubin in predicting outcome were evaluated using receiver operating characteristic curve analysis. RESULTS: Of the 153 enrolled patients, 64 (41.8%) were diagnosed with HT, of which 28 (18.3%) had sICH. In univariate analyses, DB, IDB, and TB were higher in patients with HT and sICH than in patients without. After adjustment for potential confounders, DB (odds ratio [OR], 1.364; 95% confidence interval [CI], 1.133-1.641; p = 0.001), IDB (OR, 1.143; 95% CI, 1.052-1.242; p = 0.002), and TB (OR, 1.106; 95% CI, 1.041-1.175; p = 0.001) were independently associated with HT. IDB (OR, 1.177; 95% CI, 1.064-1.303; p = 0.002) and TB (OR, 1.102; 95% CI, 1.027-1.182; p = 0.007) were independently associated with sICH. Receiver operating characteristic curve analysis showed no significant difference between the three indicators of predicting HT and sICH. CONCLUSIONS: Elevated admission bilirubin is an independent predictor of HT and sICH in AIS patients treated with MT.
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Bilirrubina/sangue , Hemorragias Intracranianas , AVC Isquêmico , Trombólise Mecânica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hemorragias Intracranianas/sangue , Hemorragias Intracranianas/diagnóstico , Hemorragias Intracranianas/etiologia , AVC Isquêmico/sangue , AVC Isquêmico/complicações , AVC Isquêmico/terapia , Masculino , Trombólise Mecânica/efeitos adversos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Estudos RetrospectivosRESUMO
The role of m6A modification in the regulation of the immune microenvironment (IME) of ischemic stroke (IS) is barely known. Thus, we aim to investigate the impact of m6A modification on the IME of IS and its diagnostic value in IS. We comprehensively assessed the m6A modification patterns, the relationship between these modification patterns and the characteristics of the IME. The m6A modification patterns of individual IS sample were quantified by m6Ascore. The performance of m6A phenotype-related genes as potential biomarkers was evaluated by the area under the receiver operating characteristic curve. Experimental validation was also performed by qRT-PCR. Six dysregulated m6A regulators were identified and a classification model consisting of four key m6A regulators (METLL3, RBMX, RBM15B, YTDHF3) could distinguish IS and healthy control samples well. METTL3 and YTHDF3 are closely related to circulating neutrophil abundance. Two distinct m6A modification patterns were determined which differed in immunocyte abundance. We also identified six m6A phenotype-related genes (APOBEC3A, PTMA, FCGR3A, LOC440926, LOC649946, and FTH1L11), and further explored their biological function. Among them, APOBEC3A, FCGR3A, and FTH1L11 were positively associated with neutrophil abundance. APOBEC3A and FCGR3A were stable diagnostic m6A-associated genes in both the discovery and validation cohorts. This study reveals that m6A modification plays a non-negligible role in the formation of a diversified and complex IME in IS. The m6A phenotype-related genes could be diagnostic biomarkers of IS.
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Adenina/análogos & derivados , Citidina Desaminase , AVC Isquêmico , Proteínas , Humanos , AVC Isquêmico/genética , Biomarcadores , Microambiente Tumoral , MetiltransferasesRESUMO
Background: Although epidemiological evidence implies a link between exposure to particulate matter (PM) and Alzheimer's disease (AD), establishing causality remains a complex endeavor. In the present study, we used Mendelian randomization (MR) as a robust analytical approach to explore the potential causal relationship between PM exposure and AD risk. We also explored the potential associations between PM exposure and other neurodegenerative diseases. Methods: Drawing on extensive genome-wide association studies related to PM exposure, we identified the instrumental variables linked to individual susceptibility to PM. Using summary statistics from five distinct neurodegenerative diseases, we conducted two-sample MR analyses to gauge the causal impact of PM on the risk of developing these diseases. Sensitivity analyses were undertaken to evaluate the robustness of our findings. Additionally, we executed multivariable MR (MVMR) to validate the significant causal associations identified in the two-sample MR analyses, by adjusting for potential confounding risk factors. Results: Our MR analysis identified a notable association between genetically predicted PM2.5 (PM with a diameter of 2.5 µm or less) exposure and an elevated risk of AD (odds ratio, 2.160; 95% confidence interval, 1.481 to 3.149; p < 0.001). A sensitivity analysis supported the robustness of the observed association, thus alleviating concerns related to pleiotropy. No discernible causal relationship was identified between PM and any other neurodegenerative diseases. MVMR analyses-adjusting for smoking, alcohol use, education, stroke, hearing loss, depression, and hypertension-confirmed a persistent causal relationship between PM2.5 and AD. Sensitivity analyses, including MR-Egger and weighted median analyses, also supported this causal association. Conclusion: The present MR study provides evidence to support a plausible causal connection between PM2.5 exposure and AD. The results emphasize the importance of contemplating air quality interventions as a public health strategy for reducing AD risk.
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Doença de Alzheimer , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Material Particulado , Material Particulado/efeitos adversos , Humanos , Doença de Alzheimer/genética , Fatores de Risco , Exposição Ambiental/efeitos adversos , Causalidade , Poluição do Ar/efeitos adversosRESUMO
BACKGROUND: It is unclear whether patients with severely disabling ischemic stroke (SDIS-that is, modified Rankin scale (mRS) scores of 3-5) benefit from non-acute endovascular recanalization (ER). OBJECTIVE: To determine the effect of non-acute ER or medical treatment in severely disabled patients with non-acute ischemic stroke (mRS scores of 3-5). METHODS: Between January 2018 and August 2021, non-acute patients with SDIS and large vessel occlusion were collected from two regional stroke centers. Patients who met the inclusion and exclusion criteria were assigned to two groups based on whether they underwent ER (ER group) or not (medical group). The primary functional outcome was the mRS score at 90 days. The primary safety outcomes were the recurrence of stroke and mortality. RESULTS: Of the 325 patients with hypoperfusion cerebral infarction caused by large vessel occlusion, 63 met the inclusion criteria (32 patients in the ER group, 31 patients in the medical group). A favorable outcome (mRS score ≤2) occurred more often in the ER group than in the medical group (59.4% vs 22.6%, respectively; OR=0.12, 95% CI 0.02 to 0.58; P<0.01). There were no significant differences in new-onset ischemic stroke (6.3% vs 3.2%, respectively; P=1.000), symptomatic intracerebral hemorrhage (12.5% vs 0%, respectively; P=0.113), or mortality within 90 days (6.3% vs 6.5%, respectively; P=1.000) between the two groups. Preoperative mRS scores (OR=7.34, 95% CI 1.56 to 34.5; P=0.02) and ER (OR=0.12, 95% CI 0.02 to 0.58; P<0.01) were significantly associated with outcome. CONCLUSION: Our data suggest that patients with SDIS (mRS score 3-5) with smaller infarct cores and better collateral circulation can benefit from non-acute ER, with no additional perioperative complications or mortality.
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Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Hemorragia Cerebral/complicações , AVC Isquêmico/complicações , Procedimentos Endovasculares/efeitos adversos , Resultado do Tratamento , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia , Trombectomia/efeitos adversos , Estudos RetrospectivosRESUMO
Background: Contrast-enhanced high-resolution magnetic resonance imaging (CE-HR-MRI) is a useful imaging modality to assess vulnerable plaques in intracranial atherosclerotic stenosis (ICAS) patients. We studied the relationship between the fibrinogen-to-albumin ratio (FAR) and plaque enhancement in patients with ICAS. Methods: We retrospectively enrolled consecutive ICAS patients who had undergone CE-HR-MRI. The degree of plaque enhancement on CE-HR-MRI was evaluated both qualitatively and quantitatively. Enrolled patients were classified into no enhancement, mild enhancement, and obvious enhancement groups. An independent association of the FAR with plaque enhancement was identified by multivariate logistic regression and receiver operating characteristic (ROC) curve analyses. Results: Of the 69 enrolled patients, 40 (58%) were classified into the no/mild enhancement group, and 29 (42%) into the obvious enhancement group. The obvious enhancement group had a significantly higher FAR than the no/mild enhancement group (7.36 vs. 6.05, p = 0.001). After adjusting for potential confounders, the FAR was still significantly independently associated with obvious plaque enhancement in multiple regression analysis (odds ratio: 1.399, 95% confidence interval [CI]: 1.080-1.813; p = 0.011). ROC curve analysis revealed that FAR >6.37 predicted obvious plaque enhancement with 75.86% sensitivity and 67.50% specificity (area under the ROC curve = 0.726, 95% CI: 0.606-0.827, p < 0.001). Conclusion: The FAR can serve as an independent predictor of the degree of plaque enhancement on CE-HR-MRI in patients with ICAS. Also, as an inflammatory marker, the FAR has potential as a serological biomarker of intracranial atherosclerotic plaque vulnerability.
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Ischemic stroke is a neurological disorder caused by vascular stenosis or occlusion, accounting for approximately 87% of strokes. Clinically, the most effective therapy for ischemic stroke is vascular recanalization, which aims to rescue neurons undergoing ischemic insults. Although reperfusion therapy is the most effective treatment for ischemic stroke, it still has limited benefits for many patients, and ischemia-reperfusion (I/R) injury is a widely recognized cause of poor prognosis. Here, we aim to investigate the mechanism of protein phosphatase Mg2+/Mn2+ dependent 1 K (PPM1K) mediates metabolic disorder of branched-chain amino acids (BCAA) by promoting fatty acid oxidation led to ferroptosis after cerebral I/R injury. We established the I/R model in mice and used BT2, a highly specific BCAA dehydrogenase (BCKD) kinase inhibitor to promote BCAA metabolism. It was further verified by lentivirus knocking down PPM1K in neurons. We found that BCAA levels were elevated after I/R injury due to dysfunctional oxidative degradation caused by phosphorylated BCKD E1α subunit (BCKDHA). Additionally, the level of phosphorylated BCKDHA was determined by decreased PPM1K in neurons. We next demonstrated that BCAA could induce oxidative stress, lipid peroxidation, and ferroptosis in primary cultured cortical neurons in vitro. Our results further showed that BT2 could reduce neuronal ferroptosis by enhancing BCAA oxidation through inhibition of BCKDHA phosphorylation. We further found that defective BCAA catabolism could induce neuronal ferroptosis by PPM1K knockdown. Furthermore, BT2 was found to alleviate neurological behavior disorders after I/R injury in mice, and the effect was similar to ferroptosis inhibitor ferrostatin-1. Our findings reveal a novel role of BCAA in neuronal ferroptosis after cerebral ischemia and provide a new potential target for the treatment of ischemic stroke.
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Ferroptose , AVC Isquêmico , Doenças Metabólicas , Traumatismo por Reperfusão , Animais , Camundongos , Aminoácidos de Cadeia Ramificada , Proteína Fosfatase 2C/genéticaRESUMO
Background: Recently, increasing evidence has implicated methylenetetrahydrofolate reductase (MTHFR) gene mutation as a risk factor for ischemic stroke (IS) in the general population. However, studies have been inconclusive and lack evidence on specific populations. We aim to determine whether the rs1801133 (NC_000001.11 (MTHFR):g. 677C>T (p.Ala222Val) variant, we termed as MTHFR rs1801133 (677 C>T), is linked to an increased risk of IS in different age groups and ancestry groups. Methods: The literature relevant to our study was found by searching the PubMed, Cochrane Library, Web of Science, EMBASE, and CNKI databases. A random effect model analysis was used to calculate the pooled odds ratio (OR) and 95% confidence interval (CI) to evaluate any possible association. We conducted a subgroup analysis based on the age and ancestry groups of the included populations. Results: As of March 2022, 1,925 citations had been identified in electronic databases, of which 96 studies involving 34,814 subjects met our eligibility criteria. A strong link was found between IS and the MTHFR gene rs1801133 (677C>T) polymorphism in all genetic models [dominant genetic model (OR = 1.47; 95%CI = 1.33-1.61; p < 0.001), recessive genetic model (OR = 1.52; 95%CI = 1.36-1.71; p < 0.001), heterozygous model (OR = 1.36; 95%CI = 1.24-1.48; p < 0.001), homozygous model (OR = 1.82; 95%CI = 1.58-2.11; p < 0.001), and T allelic genetic model (OR = 1.37; 95%CI = 1.27-1.48; p < 0.001)]. Further subgroup analyses indicated that the MTHFR rs1801133 (677C>T) variant may increase the risk of IS in Asian, Hispanic, or Latin population, middle-aged, and elderly populations (p < 0.001). Conclusion: Our results implied that mutation of the T allele of MTHFR rs1801133 (677C>T) could be a risk factor for IS. A significant association was found among Asian, Hispanic, or Latin population, middle-aged, and elderly people.
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The time window from stroke onset is critical for the treatment decision. However, in unknown onset stroke, it is often difficult to determine the exact onset time because of the lack of assessment methods, which can result in controversial and random treatment decisions. Previous studies have shown that serum biomarkers, in addition to imaging assessment, are useful for determining the stroke onset time. However, as yet there are no specific biomarkers or corresponding methodologies that are accurate and effective for determining the onset time of unknown onset stroke. Herein, we describe our novel advanced metabolites-based machine learning method (termed extreme gradient boost [XGBoost]) combined with recursive feature elimination, which accurately screened five metabolites from 1124 metabolites detected in serum. These metabolites were capable of both detecting acute ischemic stroke and backtracking the acute ischemic stroke onset time. To further investigate the pathological mechanisms of acute ischemic stroke, we also examined characteristic metabolites in different brain regions, and found two metabolites that could distinguish the core infarct area from the ischemic penumbra. Although this study is based on animal experiments, our machine learning framework and selected metabolites may provide a basis for clinical stroke evaluation and treatment.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Animais , AVC Isquêmico/diagnóstico , Isquemia Encefálica/patologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Aprendizado de Máquina , BiomarcadoresRESUMO
PURPOSE: Elderly people represent a growing stroke population with different pathophysiological states than younger. Whether intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is beneficial for elderly patients remains unclear. This study compared the efficacy and safety between elderly patients treated with MT alone and those treated with both IVT and MT. PATIENTS AND METHODS: Patients aged ≥65 years who were eligible for IVT within 4.5 h from symptom onset were selected from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke) registry, a prospective registry program for patients with endovascular treatment from 111 Chinese stroke centers. The primary efficacy outcome was the 90-day modified Rankin Scale score. We compared efficacy and safety outcomes using ordinal or binary logistic regression or a generalized linear model. RESULTS: In total, 482 elderly patients were included: 187 (38.8%) received IVT and MT (bridging MT) and 295 (61.2%) received MT alone (direct MT). There was no significant difference in the 90-day modified Rankin Scale score between the two groups (median: 4 vs 4 points, respectively; adjusted ß=-0.048, P=0.822). The direct MT group had a shorter onset-to-puncture time (225 vs 255 min, respectively; adjusted ß=-55.074, P=0.002) and a lower rate of parenchymal hemorrhage type 2 within 24 h (2.80% vs 6.63%, respectively; adjusted odds ratio [OR]=0.287, 95% confidence interval [CI]=0.096-0.856, P=0.025). In addition, the direct MT group showed a trend toward a lower incidence of sICH (5.67% vs 10.06%, adjusted OR=0.453, P=0.061), procedure-related complications (7.12% vs 12.30%, adjusted OR=0.499, P=0.052) and distal or new territorial embolization (4.07% vs 6.95%, adjusted OR=0.450, P=0.093). CONCLUSION: Direct MT had similar efficacy to bridging MT in terms of the 90-day functional outcome in elderly patients, whereas bridging MT had a longer onset-to-puncture time and increased risk of hemorrhagic transformation and procedure-related complications.
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Hemorragia Cerebral , Transtornos Cerebrovasculares , AVC Isquêmico , Trombectomia , Administração Intravenosa , Idoso , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/terapia , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/etiologia , AVC Isquêmico/cirurgia , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Melhoria de Qualidade , Trombectomia/efeitos adversos , Trombectomia/métodos , Terapia Trombolítica/métodos , Fluxo de TrabalhoRESUMO
INTRODUCTION: Limited comparative studies have reported the safety and efficacy of tirofiban in acute ischemic stroke (AIS) patients after mechanical thrombectomy (MT). Additionally, the available studies are inconsistent with each other, which makes application of tirofiban unclear in neuro-intervention. Here, we performed a comparative retrospective study to investigate whether tirofiban combined with MT improves short- and long-term prognosis in AIS patients and whether its use is associated with complications. METHOD: Retrospective data were collected for AIS patients admitted between January 2013 and January 2019 at three stroke centers. According to whether tirofiban was used during the operation, patients were divided into tirofiban group and control group. Multivariate and COX regression analyses were performed to determine the association of tirofiban treatment with safety and efficiency in subjects treated with MT. RESULT: A total of 174 patients were analyzed, of whom 89 (51.1%) were treated with tirofiban. There were no differences in the incidence of symptomatic intracerebral hemorrhage (10.2% vs. 10.6%, p=0.918), parenchymal hemorrhage type 2 (18.0% vs. 16.5%, p=0.793), and reocclusion at 24 h (3.4% vs. 10.6%, p=0.060) between the tirofiban group and control group. Multivariate regression showed that tirofiban was not associated with intracerebral hemorrhage, early neurological deterioration, neurological improvement at 7 days, functional independence at 3-month and 9-month follow-up, or death at 9-month follow-up (adjusted p > 0.05 for all). However, AIS patients treated with MT + tirofiban showed a trend towards acquiring faster functional independence, with a median time to acquire functional independence of 4.0 months compared with 6.5 months in the control group (risk ratio = 1.49, 95% confidence interval 0.98-2.27; long rank p=0.066). CONCLUSION: Tirofiban may help AIS patients given MT to gain functional independence faster, without increasing the risk of complications.
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BACKGROUND: Contrast-induced encephalopathy (CIE) is a rare disease, whose etiology and risk factors remain unclear and need investigation. METHODS: We collected 7 CIE cases from 2646 patients injected with ioversol and 5 CIE cases from 526 patients injected with iopromide, all of whom underwent neurointervention surgery in our regional centers. The incidence of CIE, its characteristics, and risks were analyzed in both groups. RESULTS: The overall incidence of CIE was 0.38%, specifically 0.95% and 0.26% in the iopromide and ioversol groups, respectively; the former incidence was significantly higher than the latter (P = 0.029). The risk of CIE with iopromide was 3.567 to 3.618 times higher than that with ioversol (single-factor analysis odds ratio [OR], 3.618; 95% confidence interval [CI], 1.144-11.443; P = 0.029; multifactor analysis OR, 3.567 (95% CI, 0.827-15.379); P = 0.088). Moreover, acute cerebral infarction was an independent risk factor for CIE (OR, 4.024; 95% CI, 1.137-14.236; P = 0.031). Contrast-induced encephalopathy could occur within 5 minutes after injecting contrast media. The CIE characteristics differed according to the medium. In the ioversol group, the most common characteristic was visual disorder (71.43%), whereas in the iopromide group, the most common characteristic was delirium (100%). CONCLUSIONS: Compared with ioversol, iopromide appeared more likely to lead to CIE. Acute cerebral infarction was an independent risk factor for CIE. The earliest CIE onset was within 5 minutes after injecting contrast. The characteristics of CIE varied significantly for different contrast media.
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Encefalopatias/epidemiologia , Iohexol/análogos & derivados , Ácidos Tri-Iodobenzoicos/efeitos adversos , Adulto , Idoso , Encefalopatias/induzido quimicamente , China/epidemiologia , Meios de Contraste/efeitos adversos , Feminino , Humanos , Incidência , Iohexol/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
PURPOSE: To investigate the utility of basi-parallel anatomic scanning magnetic resonance imaging (BPAS-MRI) for the diagnosis of vertebrobasilar artery lesions. METHOD: From October 2017-November 2018, 105 consecutive patients with abnormal configuration of the vertebrobasilar artery on time-of-flight magnetic resonance angiography (TOF-MRA) were enrolled. Conventional high-resolution MRI combined with TOF-MRA were performed to diagnose lesions and were used as the standard for sensitivity and specificity determination. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of BPAS-MRI combined with TOF-MRA were calculated. The consistencies between the two methods were evaluated by kappa test. RESULTS: Of the 105 patients, 45 were diagnosed with arteriosclerosis, 46 with vertebral artery dysplasia, 11 with artery dissection or dissecting aneurysm, and 3 as simple dilatation. Results Compared with conventional high-resolution MRI combined with TOF-MRA, for vertebrobasilar arteriosclerosis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of BPAS-MRI combined with TOF-MRA were 95.6 %, 95.0 %, 93.5 %, 96.6 % and 95.2 %, respectively and kappa value was 0.903. For vertebral artery dysplasia, they were 100 %, 96.6 %, 95.8 %, 100 %, and 98.1 %, respectively and kappa value was 0.961. For vertebrobasilar artery dissection or dissection aneurysm, they were 81.8 %, 96.8 %, 97.8 %, 75.0 % and 95.2 %, respectively and kappa value was 0.756. CONCLUSIONS: BPAS-MRI can show the outer contour of the vertebrobasilar artery system. Combined with TOF-MRA, it may be used to differentiate among vertebrobasilar artery abnormalities, and be used in hospitals where conventional high-resolution MRI is not feasible.
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Artéria Basilar/diagnóstico por imagem , Doenças Arteriais Intracranianas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Artéria Vertebral/diagnóstico por imagem , Idoso , Artéria Basilar/patologia , Diagnóstico Diferencial , Feminino , Humanos , Doenças Arteriais Intracranianas/patologia , Angiografia por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Artéria Vertebral/patologiaRESUMO
Blood-brain barrier (BBB) dysfunction is involved in the pathogenesis of contrast-induced encephalopathy (CIE), which is a rare adverse event following angiography. In this study, we observed the dynamic effect and potential mechanism of ioversol on the BBB in rats. Eighty-one healthy rats were randomly divided into a normal control group (n = 9), ioversol group (n = 36), and 0.9% NaCl group (n = 36); the latter two groups were separately subdivided into four groups based on time points after treatment (0.5, 3, 6, and 24 h) (n = 9/group). Permeability of the BBB was measured by an Evans Blue (EB) assay. Levels of the tight junction (TJ) proteins ZO-1 and occludin were determined by western blot and immunofluorescence staining. EB content increased at 3 h after the administration of ioversol via the carotid artery and reached a peak at 6 h (P < 0.05), whereas it decreased to its normal level at 24 h. Western blot and immunofluorescence staining indicated that the expression of ZO-1 in brain tissues gradually decreased to its lowest level at 3 h, and then increased gradually, but was still lower than that of the normal control group at 24 h (P < 0.05). Occludin was similar, but its lowest expression appeared at 0.5 h. This study demonstrated that the permeability of BBB in rats increased first and then decreased after ioversol was injected into the carotid artery. The mechanism may be related to altered protein expression of TJs, which are important structures in BBB. Early intervention against TJ proteins may be an effective measure to prevent and treat CIE.
Assuntos
Barreira Hematoencefálica/metabolismo , Permeabilidade Capilar , Meios de Contraste/farmacologia , Ocludina/metabolismo , Ácidos Tri-Iodobenzoicos/farmacologia , Proteína da Zônula de Oclusão-1/metabolismo , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Masculino , Ocludina/genética , Ratos , Ratos Sprague-Dawley , Proteína da Zônula de Oclusão-1/genéticaRESUMO
AIMS: Edaravone potentially alleviates cognitive deficits in a mouse model of Alzheimer's disease (AD). However, the mechanism of edaravone in suppressing AD progression remains unclear. We aim to investigate the mechanism of edaravone in suppressing oxidative stress-mediated AD progression in vitro. MAIN METHODS: Human neuroblastoma SH-SY5Y cells were pretreated with different concentrations of edaravone prior to the induction by Aß25-35. Cell viability, apoptosis, reactive oxygen species, and expression of antioxidative response elements (ARE) including Nrf2, SOD, and HO-1 were assessed. KEY FINDINGS: The results showed that apoptosis and reactive oxygen species levels significantly increased in Aß25-35-treated cells, whereas the mRNA and protein levels of Nrf2, SOD and HO-1 decreased. The opposite changes were observed in cells that were pre-treated with edaravone, particularly at a concentration of 40⯵M. Aß25-35-treatment suppressed Nrf2 expression and nuclear translocation were rescued by Edaravone. Genetic inhibition of Nrf2 greatly decreased the protective effect of edaravone against cell apoptosis and cytotoxicity induced by Aß25-35, accompanied by decreases in SOD and HO-1 expression. SIGNIFICANCE: Activation of the Nrf2/ARE signaling pathway may underlie the protective effects of edaravone against the oxidative damage associated with Alzheimer's disease.