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1.
Medicine (Baltimore) ; 99(11): e19143, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32176040

RESUMEN

BACKGROUND: To explore the correlation between recurrent risk and CYP2C19 gene polymorphisms in patients with ischemic stroke (IS) treated with clopidogrel for prevention. METHODS: A total of 289 patients with IS treated with clopidogrel regularly were enrolled in this study, and stroke recurrence of all patients were recorded by follow-up. The correlation between CYP2C19 gene polymorphism and stroke recurrence in patients taking clopidogrel regularly was analyzed. RESULTS: After a mean follow-up period of 6 months, there were 289 patients who took clopidogrel regularly, and 41 of which occurred recurrent stroke. Patients of poor metabolizer and intermediate metabolizer had higher risk of recurrent stroke comparing with patients of extensive metabolize, and the odds ratios were 2.88 (95% confidence interval [CI] 1.31-6.33, P = .068) and 3.00 (95% CI 1.09-8.22, P = .027), respectively. The recurrence risk of *2 (G681A)A allele carriers was 3.30 times that of G allele carriers (P = .0065). The recurrence rate of stroke in patients carrying heterozygous and homozygous *2 allele mutant was 1.96 times (P = .071) and 3.30 times (P = .012) that of patients with wild-type genes. Multifactor logistic regression analysis result indicated carrying loss of function (LOF) allele was an independent risk factor of stroke recurrence. CONCLUSION: For patients with IS treated with clopidogrel regularly for secondary prevention, poor metabolizer, and intermediate metabolizer patients had higher risk of recurrent stroke comparing with extensive metabolize ones. Carrying CYP2C19 LOF allele is an independent risk factor of stroke recurrence in patients with IS.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Clopidogrel/uso terapéutico , Citocromo P-450 CYP2C19/genética , Inhibidores de Agregación Plaquetaria/uso terapéutico , Prevención Secundaria/métodos , Accidente Cerebrovascular/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/etiología , Isquemia Encefálica/genética , Clopidogrel/metabolismo , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/metabolismo , Polimorfismo Genético , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/genética
2.
Medicine (Baltimore) ; 99(7): e18995, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32049794

RESUMEN

AIM: To determine the risk factors related to hemorrhagic transformation in Chinese patients with acute ischemic stroke treated with intravenous thrombolysis. METHODS: Studies published in different languages were retrieved by systematically searching PubMed, EMBASE, Vip, CNKI, and WanFang Data from the establishment of the library to December 31, 2018, as well as manually examining the references of the original articles. The outcome measures of efficacy covered risk factors. Safety evaluation was measured by relative ratio of complications. RESULTS: A total of 36 studies involving 5597 participants were covered in this meta-analysis. The results indicated that age [WMD = 2.44, 95% CI (1.39,3.48)], male [OR = 1.21, 95% CI (1.02, 1.44)], diabetes [OR = 2.05, 95%CI (1.72,2.44)], atrial fibrillation [OR = 2.85, 95%CI (2.40, 3.39)], previous stroke [OR = 1.8, 95%CI (1.33, 2.44)], onset to treatment time (OTT) [WMD = 3.74, 95%CI (2.91, 4.58)], National Institute of Health stroke scale scores (NIHSS) [WMD = 4.17, 95% CI (3.37, 4.97)], infarct size [WMD = 4.11, 95% CI (3.15, 5.37)], ischemic signs of computed tomography (CT) [OR = 3.49, 95%CI (2.47, 4.93)] were associated with increased risk of hemorrhagic transformation after intravenous thrombolysis. CONCLUSION: The systematic review showed that male, age, diabetes, NIHSS, OTT, atrial fibrillation, post stroke, infarct size, and ischemic signs of CT were significantly correlated with hemorrhagic transformation (HT). PROSPERO REGISTRATION NUMBER: CRD42019127499.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Hemorragia Cerebral/epidemiología , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/métodos , Administración Intravenosa , Factores de Edad , China , Femenino , Humanos , Masculino , Factores Sexuales
3.
Medicine (Baltimore) ; 99(2): e18568, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31914035

RESUMEN

OBJECTIVE: Ginkgo biloba extract (GBE) is widely used as an adjunctive treatment for ischemic stroke. This meta-analysis aimed to evaluate the effectiveness and safety of GBE specifically for long-term users at the convalescence stage of ischemic stroke. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials, Embase Database, WHO Clinical Trials Registration Platform, Chinese National Knowledge Infrastructure, Wanfang Database, and Chinese Scientific Journal Database were searched from inception to 20 September 2018. Risk ratio (RR) and mean difference (MD) with a 95% confidence interval (CI) were used as effect estimates using RevMan software (5.3; Review Manager [RevMan], Nordic Cochrane Centre, Copenhagen, Denmark). A meta-analysis was performed where data were available. A trial sequential analysis was used to control random errors for recurrence rate and the GRADE (grading of recommendations, assessment, development, and evaluations) approach was used to assess the quality of the body of evidence. The meta-analysis design was registered on PROSPERO (CRD42018110211, http://www.crd.york.ac.uk/PROSPERO). RESULTS: We identified 15 randomized clinical trials involving 1829 participants. The majority of the included trials were of high risk of bias in methodological quality. For acute ischemic stroke, adding GBE to conventional therapy led to higher Barthel index scores (MD: 5.72; 95% CI: 3.11-8.33) and lower neurological function deficit scores (MD: -1.39; 95% CI: -2.15 to -0.62). For patients in their convalescence (or sequelae) stage of ischemic stroke, GBE was superior in improving dependence (MD: 7.17; 95% CI: 5.96-8.38) and neurological function deficit scores (MD: -1.15; 95% CI: -1.76 to -0.53) compared with placebo or conventional therapy, but there was no difference in vascular events (RR: 0.70; 95% CI: 0.44-1.14), recurrence rate (RR: 0.57; 95% CI: 0.26-1.25; trial sequential analysis: conclusive) and mortality (RR: 1.07; 95% CI: 0.41-2.81). CONCLUSIONS: GBE appears to improve neurological function and dependence compared with conventional therapy for ischemic stroke at different stages and appears generally safe for clinical application. The lack of improvement in recurrence rate was confirmed by trial sequential analysis. Due to the generally weak evidence, further large, rigorous trials are warranted.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Quimioterapia Adyuvante , Humanos , Fitoterapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia
4.
N Engl J Med ; 382(1): 9, 2020 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-31738483

RESUMEN

BACKGROUND: The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied. METHODS: In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes. RESULTS: A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups. CONCLUSIONS: After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.).


Asunto(s)
Anticolesterolemiantes/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , LDL-Colesterol/sangre , Ezetimiba/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Ataque Isquémico Transitorio/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Adulto , Anciano , Anticolesterolemiantes/efectos adversos , Aterosclerosis/complicaciones , Aterosclerosis/tratamiento farmacológico , Isquemia Encefálica/tratamiento farmacológico , Enfermedades Cardiovasculares/mortalidad , Quimioterapia Combinada , Femenino , Humanos , Análisis de Intención de Tratar , Ataque Isquémico Transitorio/complicaciones , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/sangre
5.
World Neurosurg ; 133: e835-e841, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31614218

RESUMEN

BACKGROUND: Several independent randomized controlled trials have shown superior efficacy of mechanical thrombectomy (MT) for management of acute ischemic stroke (AIS). However, elderly patients have been underrepresented or excluded in these trials. The aim of this study was to investigate the feasibility and safety of MT in patients with AIS ≥90 years old. METHODS: A retrospective review was performed of patients ≥90 years old presenting with AIS who underwent MT between 2010 and 2018. RESULTS: Of 453 patients with AIS, 5.74% (n = 26) were ≥90 years old, and 69.32% (n = 314) were 60-89 years old. Of baseline characteristics between both groups, there was a significant difference in age, sex, body mass index, smoking, hyperlipidemia, atrial fibrillation, and diabetes mellitus. Mean National Institutes of Health Stroke Scale score on admission was higher in the nonagenarians (17 vs. 15). Similar proportions of both groups received tissue plasminogen activator, 57.69% (n = 15) versus 42.68% (n = 134), P = 0.14). There was no difference in periprocedural and postprocedural complications, good Thrombolysis In Cerebral Infarction scores (88.46% [n = 23] vs. 87.58% [n = 275], P = 1.00), good modified Rankin Scale scores (34.62% [n = 4] vs. 49.36% [n = 155], P = 0.40), or mortality (11.54% [n = 3] vs. 13.06% [n = 41], P = 0.82). CONCLUSIONS: Age is a factor that affects functional outcome following MT. Advancements in catheter techniques, technical experience, and great outcomes with MT allow for pushing the boundaries to consider age as one factor, rather than an exclusion criterion. Our results show that MT is safe and feasible in nonagenarians.


Asunto(s)
Isquemia Encefálica/cirugía , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Factores de Edad , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/tratamiento farmacológico , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del Tratamiento
6.
World Neurosurg ; 133: 150-154, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31589986

RESUMEN

BACKGROUND: Pseudoaneurysm after mechanical thrombectomy (MT) is rare but is one of the potential complications associated with endovascular procedures. There is limited information regarding its mechanism of formation and the potential risk of delayed bleeding. CASE DESCRIPTION: An 84-year-old woman was admitted to our institution with right hemiplegia and global aphasia. Magnetic resonance imaging and angiography revealed occlusion of the M2 segment of the left middle cerebral artery with subtle acute ischemic change in this territory. After initiating intravenous thrombolysis, MT was performed for persistent occlusion of the M2. Successful revascularization was finally achieved with a single pass of a Trevo XP 3 mm × 20 mm stent retriever; significant deviation of the vessel occurred during withdrawal of the stent retriever. Anticoagulation was initiated after confirming resolution of a small amount of postprocedural subarachnoid hemorrhage 1 day after the procedure. However, 4 days after the procedure, computed tomography and angiography revealed a massive sylvian hematoma with de novo formation of a small pseudoaneurysm at the site where the stent retriever was deployed. Open surgery revealed a small artery avulsion at this site. The lesion was closed by microsurgical suturing. CONCLUSIONS: Angiographic and intraoperative findings showed that the mechanism of formation of the pseudoaneurysm was small artery avulsion resulting from deviation of the vessel during withdrawal of the stent retriever. When performing MT in a tortuous distal vessel, the possibility of small artery avulsion should be kept in mind to both prevent and manage critical hemorrhagic complications.


Asunto(s)
Aneurisma Falso/etiología , Isquemia Encefálica/terapia , Revascularización Cerebral/efectos adversos , Trombectomía/efectos adversos , Anciano de 80 o más Años , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/cirugía , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , Microcirugia , Procedimientos Neuroquirúrgicos , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Stents , Resultado del Tratamiento
7.
World Neurosurg ; 133: e267-e274, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31505293

RESUMEN

OBJECTIVE: Decompressive craniectomy (DC) has been advocated as a lifesaving procedure in management of patients with raised intracranial pressure due to malignant ischemic stroke (MIS). The aim of this study was to identify comparative radiologic parameters after DC to predict functional outcome at 6 months in patients with MIS. METHODS: A retrospective analysis (2015-2018) of patients (median age 54 years; range, 29-80 years) with MIS who underwent postoperative computed tomography within 24 hours of DC was performed. Multivariate regression analysis was computed to predict clinical outcome at 6 months based on the Glasgow Coma Outcome Scale Extended. RESULTS: With median National Institutes of Health Stroke Scale score of 20 (range, 3-33), mean preoperative stroke volume was 250 ± 75 cm3. Median Glasgow Coma Outcome Scale Extended score at 6 months was 4. Multivariate regression analysis showed that the comparative radiographic characteristics of absence of effacement of cortical sulci (odds ratio 2.88; 95% confidence interval, 1.22-20.71; P = 0.02), absence of hemorrhagic transformation (odds ratio 1.09; 95% confidence interval, 1.99-12.89; P = 0.03), and absence of compression of lateral ventricles (odds ratio 3.75; 95% confidence interval, 1.28-22.4; P = 0.05) on postoperative computed tomography scan were significant independent predictors of good functional outcome (Glasgow Coma Outcome Scale Extended score 5-8). CONCLUSIONS: The comparative radiographic characteristics of absence of effacement of cortical sulci, hemorrhagic transformation, and compression of the lateral ventricles after DC in patients with MIS bore a significant relationship to predicting clinical outcome at 6 months.


Asunto(s)
Isquemia Encefálica/diagnóstico por imagen , Craniectomía Descompresiva/métodos , Hipertensión Intracraneal/cirugía , Neuroimagen , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/etiología , Isquemia Encefálica/complicaciones , Isquemia Encefálica/tratamiento farmacológico , Femenino , Fibrinolíticos/uso terapéutico , Escala de Consecuencias de Glasgow , Humanos , Hipertensión Intracraneal/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Terapia Trombolítica , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del Tratamiento
8.
J Stroke Cerebrovasc Dis ; 29(2): 104515, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31786042

RESUMEN

BACKGROUND: Many acute ischemic stroke (AIS) patients present with unknown time of symptom onset (UTO). In these situations, wake-up MRI protocols can guide treatment decisions: patients with DWI (diffusion-weighted imaging) but no fluid-attenuated inversion recovery lesion were shown to benefit from IVT (intravenous thrombolysis). However, initial MRI of some stroke patients is DWI negative, leaving it unclear whether this subgroup profits from IVT. Therefore, we aimed to compare the safety and efficacy of IVT in wake-up AIS patients with or without a DWI lesion in initial imaging. METHODS: We performed a case-control study. All AIS patients with UTO who underwent wake-up MRI and were treated with IVT at a German University Hospital from 2013 to 2017 were included. Patients without (DWI-) were compared to patients with DWI lesion (DWI+) regarding clinico-radiological characteristics, adverse events, and outcome at discharge. Likely stroke mimics were excluded. RESULTS: Eleven DWI- and 32 DWI+ patients were included. There were no statistically significant differences regarding functional scores, age, sex, door-to-needle time, bleeding complications, and death. DWI+ patients more frequently had anterior circulation stroke (P = .049) and higher modified Rankin Scale (mRS) scores at discharge (P = .048). Solely in the DWI+ group 3 bleeding complications (2 asymptomatic hemorrhagic transformations, 1 muscle hematoma) and 3 deaths occurred (P = .29). A favourable outcome (mRS≤ 2) was achieved in 82% of the DWI- and in 58% of the DWI+ group (p > .05). CONCLUSIONS: Our data suggest that IVT may be used in DWI- patients with UTO with acute neurological symptoms very likely to be related to AIS.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Imagen de Difusión por Resonancia Magnética , Fibrinolíticos/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/fisiopatología , Toma de Decisiones Clínicas , Técnicas de Apoyo para la Decisión , Evaluación de la Discapacidad , Femenino , Fibrinolíticos/efectos adversos , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Selección de Paciente , Valor Predictivo de las Pruebas , Recuperación de la Función , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/fisiopatología , Terapia Trombolítica/efectos adversos , Factores de Tiempo , Tiempo de Tratamiento , Resultado del Tratamiento
9.
J Stroke Cerebrovasc Dis ; 29(2): 104526, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31836356

RESUMEN

BACKGROUND AND PURPOSE: Early neurologic improvement (ENI) in patients treated with alteplase has been shown to correlate with functional outcome. However, the definition of ENI remains controversial and has varied across studies. We hypothesized that ENI defined as a percentage change in the National Institute of Health Stroke Scale (NIHSS) score (percent change NIHSS score) at 24-hours would better correlate with favorable outcomes at 3 months than ENI defined as the change in NIHSS score (delta NIHSS score) at 24 hours. METHODS: Retrospective analysis of prospectively collected single-center quality improvement data was performed of all acute ischemic stroke (AIS) patients treated with alteplase. We examined delta NIHSS score and percent change NIHSS score in unadjusted and adjusted logistic regression models as predictors of a favorable outcome at 3 months (defined as mRS 0-1). RESULTS: Among 586 patients who met the inclusion criteria, 194 (33.1%) had a favorable outcome at 3 months. In fully adjusted models, both delta NIHSS score (OR per point decrease 1.27; 95% confidence interval [CI] 1.19-1.36) and percent change NIHSS score (OR per 10 percent decrease 1.17; 95% CI 1.12-1.22) were associated with favorable functional outcome at 3 months. Receiver operating characteristic (ROC) curve comparison showed that the area under the ROC curve for percent change NIHSS score (.755) was greater than delta NIHSS score (.613) or admission NIHSS (.694). CONCLUSIONS: Percentage change in NIHSS score may be a better surrogate marker of ENI and functional outcome in AIS patients after receiving acute thrombolytic therapy. More studies are needed to confirm our findings.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Fibrinolíticos/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica , Activador de Tejido Plasminógeno/administración & dosificación , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatología , Evaluación de la Discapacidad , Femenino , Fibrinolíticos/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Recuperación de la Función , Reproducibilidad de los Resultados , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/fisiopatología , Terapia Trombolítica/efectos adversos , Factores de Tiempo , Activador de Tejido Plasminógeno/efectos adversos , Resultado del Tratamiento
10.
J Stroke Cerebrovasc Dis ; 29(2): 104562, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31836361

RESUMEN

INTRODUCTION: Recent studies have indicated that the damaging effects of stroke are not only limited to the brain. We sought to examine the changes of liver and renal enzymes in the acute phase of ischemic stroke and to investigate possible explanations and therapeutic options, concerning in particular the functional alterations of peripheral organs after administration of an anti-inflammatory agent. MATERIAL/METHODS: Twelve-week-old Wistar male rats were randomly divided into control and Cyclosporine groups (n = 10 each). Cyclosporine was given orally by gavage for 5 days prior to cerebral ischemia at a total volume of 15 mg/kg/day. All animals were subjected to 60 minutes focal ischemia by filament occlusion of the middle cerebral artery. Serum concentrations of Creatinine, Urea, SGOT, SGPT, and γGT were determined at the time before surgery and after 60 minutes brain ischemia. RESULTS: Comparing data of 2 time-points, in both groups the serum liver enzyme levels increased progressively during the ischemic period. The liver enzymes and Urea were significantly lower in the Cyclosporine group than in the control group and the levels of Creatinine were slightly higher in the Cyclosporine group, in both time-points. CONCLUSIONS: The detection of high liver enzyme serum levels in the acute phase of ischemic stroke implies the secondary effect of cerebral infraction on the peripheral organs and particularly on the liver function. Cyclosporine seems to exhibit a protective activity and to affect both liver and renal function after ischemic stroke.


Asunto(s)
Antiinflamatorios/farmacología , Isquemia Encefálica/tratamiento farmacológico , Ciclosporina/farmacología , Enfermedades Renales/prevención & control , Riñón/efectos de los fármacos , Hepatopatías/prevención & control , Hígado/efectos de los fármacos , Accidente Cerebrovascular/tratamiento farmacológico , Animales , Biomarcadores/sangre , Isquemia Encefálica/sangre , Isquemia Encefálica/complicaciones , Isquemia Encefálica/fisiopatología , Modelos Animales de Enfermedad , Riñón/enzimología , Riñón/fisiopatología , Enfermedades Renales/sangre , Enfermedades Renales/etiología , Enfermedades Renales/fisiopatología , Hígado/enzimología , Hígado/fisiopatología , Hepatopatías/sangre , Hepatopatías/etiología , Hepatopatías/fisiopatología , Masculino , Ratas Wistar , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/fisiopatología , Factores de Tiempo
11.
Acta Neurochir Suppl ; 127: 47-54, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31407062

RESUMEN

BACKGROUND: Previously studies have shown that Nox2 and Nox4, as members of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase, Nox), participate in brain damage caused by ischemia-reperfusion (I/R). The aim of this study is to investigate the effects of specific chemical inhibitors of Nox2 and Nox4 on cerebral I/R-induced brain injury in rats. METHODS: At 0.5 h before MCAO surgery, the rats were pretreated with vehicle, Nox2 inhibitor (gp91ds-tat), and Nox4 inhibitor (GKT137831), respectively. After reperfusion for 24 h, the infarct sizes of brain tissues in rats in various groups are determined. The penumbra (ischemic) tissues are collected to measure ROS levels, neuronal apoptosis, and degeneration, as well as the integrity of the blood-brain barrier (BBB) in brain tissues of rats. RESULTS: gp91ds-tat and GKT137831 pretreatment significantly reduced the infarct sizes in brain tissues of rats, effectively suppressed I/R-induced increase in ROS levels, neuronal apoptosis and degeneration, and obviously alleviated BBB damage. CONCLUSION: Under cerebral I/R conditions, Nox2 inhibitor (gp91ds-tat) and Nox4 inhibitor (GKT137831) can effectively play a protective role in the brain tissues of rats.


Asunto(s)
Lesiones Encefálicas , Isquemia Encefálica , NADPH Oxidasa 2 , NADPH Oxidasa 4 , Daño por Reperfusión , Animales , Apoptosis/efectos de los fármacos , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , NADPH Oxidasa 2/antagonistas & inhibidores , NADPH Oxidasa 2/metabolismo , NADPH Oxidasa 4/antagonistas & inhibidores , NADPH Oxidasa 4/metabolismo , NADPH Oxidasas , Ratas , Especies Reactivas de Oxígeno , Daño por Reperfusión/metabolismo
12.
Zh Nevrol Psikhiatr Im S S Korsakova ; 119(10): 134-140, 2019.
Artículo en Ruso | MEDLINE | ID: mdl-31793555

RESUMEN

The results of the analysis of comparative studies of neurotrophic drugs based on brain hydrolysates (BH) are presented. The most comprehensive comparative study of the BH drugs carried out by Zhang, et al. 2019 investigated the effects of four drugs (cognistar, cerebrolysate, cortexin, cerebrolysin) on a model of ischemic stroke in rats. The study showed that a significant improvement in the neurological outcome compared with placebo was observed only with cerebrolysin. Higher standardization in elemental composition, higher antioxidant activity, and presence of active peptide fragments of neuropeptides of nerve growth factor, enkephalins, orexin and galanin in cerebrolysin explains neurotrophic and neuroprotective effects of the drug.


Asunto(s)
Isquemia Encefálica , Fármacos Neuroprotectores , Accidente Cerebrovascular , Animales , Encéfalo/efectos de los fármacos , Isquemia Encefálica/tratamiento farmacológico , Galanina , Fármacos Neuroprotectores/uso terapéutico , Ratas , Accidente Cerebrovascular/tratamiento farmacológico
13.
Zh Nevrol Psikhiatr Im S S Korsakova ; 119(8. Vyp. 2): 84-89, 2019.
Artículo en Ruso | MEDLINE | ID: mdl-31825367

RESUMEN

The high prevalence and disability of patients with ischemic stroke make the further development of the rehabilitation system relevant. The implementation of neuroplasticity mechanisms is largely provided by neurotrophic factors. One of the most well-known neurotrophic drugs is cerebrolysin, the efficacy of which in patients with stroke has been confirmed in many clinical studies. A recent meta-analysis included 9 randomized, double-blind, placebo-controlled clinical studies of using cerebrolysin in 1879 patients with hemispheric ischemic stroke, where it was administered at a dose of 30-50 ml for at least 1 week (10-21 days) and therapy was started during 72 hours after stroke. Cerebrolysin has been shown to give patients a 60% chance of better outcomes after a stroke, improves early recovery and increases the likelihood of better recovery.


Asunto(s)
Isquemia Encefálica , Fármacos Neuroprotectores , Accidente Cerebrovascular , Isquemia Encefálica/tratamiento farmacológico , Método Doble Ciego , Humanos , Fármacos Neuroprotectores/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular/tratamiento farmacológico , Resultado del Tratamiento
14.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4800-4805, 2019 Nov.
Artículo en Chino | MEDLINE | ID: mdl-31872585

RESUMEN

Due to the increasing incidence of central nervous system diseases,especially the increasing incidence and mortality of stroke,brain-targeted drug delivery has attached more and more attention. Nasal administration,as one of the ways of brain-targeted administration,can effectively make the drug delivered to the brain in a targeted way after by passing the blood-brain barrier,providing a new idea for the treatment of central nervous system diseases. Therefore,it is a promising administration way. In recent years,the treatment of encephalopathy by nasal administration of traditional Chinese medicine has become a hot topic in the research of traditional Chinese medicine. Ischemic stroke is one of the most important diseases endangering human health. Nasal administration has a history of thousands of years in treatment of stroke. Modern medical research has proved that there is a subtle connection between the nasal cavity and the brain,and the complex and ingenious structure of the nasal cavity provides the possibility for drugs delivery to the brain through the nose. Drug administration through nasal cavity has obvious advantages in treatment of central nervous system diseases represented by ischemic stroke. Nasal administration is characterized by non-invasion,low infection,rapid absorption and brain targeting. The author will expound the theoretical basis of brain targeting of nasal administration from the aspects of anatomy and physiology,and summarize the transport pathway of drugs through the nose into the brain,the in vitro and in vivo experimental research basis of the " nose-brain"pathway,and the clinical nasal administration of traditional Chinese medicine to prevent cerebral ischemia. It provides a reference for better research of drugs to prevent and treat cerebral ischemia injury through the " nose-brain"pathway and lays a foundation for further research of the " nose-brain" pathway.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Medicina China Tradicional , Preparaciones Farmacéuticas , Administración Intranasal , Encéfalo , Sistemas de Liberación de Medicamentos , Humanos , Mucosa Nasal
15.
Cardiovasc Ther ; 2019: 1607181, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31867054

RESUMEN

Aim: Though combination of clopidogrel added to aspirin has been compared to aspirin alone in patients with stroke or transient ischemic attack, limited data exists on the relative efficacy and safety between clopidogrel and aspirin monotherapy in patients with a recent ischemic stroke. We aimed to compare clopidogrel versus aspirin monotherapy in this population. Methods: PubMed, Embase, and CENTRAL databases were searched from inception to May 2018 to identify clinical trials and observational studies comparing clopidogrel versus aspirin for secondary prevention in patients with recent ischemic stroke within 12 months. Pooled effect estimates were calculated using a random effects model and were reported as risk ratios with 95% confidence intervals. Results: Five studies meeting eligibility criteria were included in the analysis. A total of 29,357 adult patients who had recent ischemic stroke received either clopidogrel (n = 14, 293) or aspirin (n = 15, 064) for secondary prevention. Pairwise meta-analysis showed a statistically significant risk reduction in the occurrence of major adverse cardiovascular and cerebrovascular events (risk ratio 0.72 [95% CI, 0.53-0.97]), any ischemic or hemorrhagic stroke (0.76 [0.58, 0.99), and recurrent ischemic stroke (0.72 [0.55, 0.94]) in patients who received clopidogrel versus aspirin. The risk of bleeding was also lower for clopidogrel versus aspirin (0.57 [0.45, 0.74]). There was no difference in the rate of all-cause mortality between the two groups. Conclusions: The analysis showed lower risks of major adverse cardiovascular or cerebrovascular events, recurrent stroke, and bleeding events for clopidogrel monotherapy compared to aspirin. These findings support clinical benefit for single antiplatelet therapy with clopidogrel over aspirin for secondary prevention in patients with recent ischemic stroke.


Asunto(s)
Aspirina/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Clopidogrel/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Prevención Secundaria/métodos , Accidente Cerebrovascular/tratamiento farmacológico , Aspirina/efectos adversos , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidad , Clopidogrel/efectos adversos , Hemorragia/inducido químicamente , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Recurrencia , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidad , Factores de Tiempo , Resultado del Tratamiento
16.
Stroke ; 50(8): 2147-2155, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31860411

RESUMEN

Background and Purpose- Intravenous administration of heparin during endovascular treatment for ischemic stroke may improve outcomes. However, risks and benefits of this adjunctive therapy remain uncertain. We aimed to evaluate periprocedural intravenous heparin use in Dutch stroke intervention centers and to assess its efficacy and safety. Methods- Patients registered between March 2014 and June 2016 in the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke), including all patients treated with endovascular treatment in the Netherlands, were analyzed. The primary outcome was functional outcome (modified Rankin Scale) at 90 days. Secondary outcomes were successful recanalization (extended Thrombolysis in Cerebral Infarction ≥2B), symptomatic intracranial hemorrhage, and mortality at 90 days. We used multilevel regression analysis to evaluate the association of periprocedural intravenous heparin on outcomes, adjusted for center effects and prognostic factors. To account for possible unobserved confounding by indication, we analyzed the effect of center preference to administer intravenous heparin, defined as percentage of patients treated with intravenous heparin in a center, on functional outcome. Results- One thousand four hundred eighty-eight patients from 16 centers were analyzed, of whom 398 (27%) received intravenous heparin (median dose 5000 international units). There was substantial between-center variability in the proportion of patients treated with intravenous heparin (range, 0%-94%). There was no significant difference in functional outcome between patients treated with intravenous heparin and those without (adjusted common odds ratio, 1.17; 95% CI, 0.87-1.56), successful recanalization (adjusted odds ratio, 1.24; 95% CI, 0.89-1.71), symptomatic intracranial hemorrhage (adjusted odds ratio, 1.13; 95% CI, 0.65-1.99), or mortality (adjusted odds ratio, 0.95; 95% CI, 0.66-1.38). Analysis at center level showed that functional outcomes were better in centers with higher percentages of heparin administration (adjusted common odds ratio, 1.07 per 10% more heparin, 95% CI, 1.01-1.13). Conclusions- Substantial between-center variability exists in periprocedural intravenous heparin use during endovascular treatment, but the treatment is safe. Centers using heparin more often had better outcomes. A randomized trial is needed to further study these effects.


Asunto(s)
Anticoagulantes/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Procedimientos Endovasculares/métodos , Fibrinolíticos/uso terapéutico , Heparina/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Activador de Plasminógeno de Tipo Uroquinasa/uso terapéutico , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Quimioterapia Combinada , Femenino , Heparina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Resultado del Tratamiento
17.
Life Sci ; 239: 117036, 2019 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-31697951

RESUMEN

AIMS: Previous literature has shown that melatonin plays a critical role in protecting against cerebral ischemia/reperfusion (I/R) injury. Sirtuin3(SIRT3), as one member of the sirtuin family, protects against oxidative stress-related diseases. However, the association between melatonin and SIRT3 in cerebral I/R injury is not well understood. Our experiment was planned to investigate whether melatonin protects against cerebral I/R injury through SIRT3 activation. MAIN METHODS: We selected transient middle cerebral artery occlusion (tMCAO) mice as the model of cerebral I/R injury. Male C57/BL6 mice were pre-treated with or without a selective SIRT3 inhibitor and then subjected to tMCAO surgery. Melatonin (20 mg/kg) was given to mice by intraperitoneal injection after ischemia and before reperfusion. Then, we observed the changes in the SIRT3 and downstream relative proteins, infarction volume, neurological score, Nissl, H&E and TUNEL staining, and the expression of apoptosis proteins after tMCAO. KEY FINDINGS: Melatonin upregulated the expression of SIRT3 after tMCAO, and alleviated the neurological dysfunction and cell apoptosis through SIRT3 activation. SIGNIFICANCE: Our research proved that melatonin promoted SIRT3 expression after tMCAO and alleviated cerebral I/R injury by activating the SIRT3 signaling pathway. This study provides novel therapeutic targets and mechanisms for the treatment of ischemic stroke in the clinic, especially during cerebrovascular reperfusion.


Asunto(s)
Melatonina/farmacología , Daño por Reperfusión/metabolismo , Sirtuina 3/metabolismo , Animales , Apoptosis/efectos de los fármacos , Isquemia Encefálica/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Masculino , Melatonina/metabolismo , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Sirtuina 3/fisiología , Accidente Cerebrovascular/tratamiento farmacológico
18.
Medicine (Baltimore) ; 98(46): e17864, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31725629

RESUMEN

INTRODUCTION: Ischemic stroke is an extremely rare disorder in children. The timely diagnosis is essential for the outcome of these children, but unfortunately, delays in diagnosis occur frequently. PATIENT CONCERNS: We report the case of a 7-month-old infant admitted in our clinic for limited movements of the superior and inferior right limbs whose onset was 27 hours before with repeated clonic movements of the right hand associated with the same manifestations in the right oral commissure lasting approximately 10 seconds. DIAGNOSIS: The laboratory tests revealed high D-dimers, and positive IgG anti-cardiolipin and anti-beta2 glycoproteins I antibodies, whereas the genetic profile for thrombophilia revealed heterozygote mutation in MTHFR C677T and A1298C genes. Brain imaging established the diagnosis of left frontal ischemic stroke, frontal ischemic stroke, hypoplasia of internal carotid artery, and agenesia of segment M1 of median cerebral artery and segment A1 of left anterior cerebral artery. INTERVENTION: We administered low-molecular-weight heparin, antiplatelet therapy along with vasodilators and depletive treatment, wide-spectrum antibiotics, and anticonvulsant therapy. OUTCOME: The neurological deficit was greatly improved, especially in the inferior limb after 6 month from the incident of stroke, and all laboratory parameters were within normal limits including the antibodies mentioned above. CONCLUSION: Cerebral vascular malformation, excessive weight, and altered lipid profiles contributed to the development of acute ischemic stroke in our patient.


Asunto(s)
Isquemia Encefálica/diagnóstico , Accidente Cerebrovascular/diagnóstico , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/fisiopatología , Humanos , Lactante , Factores de Riesgo , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/fisiopatología
19.
BMC Neurol ; 19(1): 300, 2019 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-31771530

RESUMEN

BACKGROUND: The benefit of intravenous thrombolysis (IVT) for acute ischemic stroke is time dependent. Despite great effort, the median door-to-needle time (DNT) was 60 min at the United States stroke centers. We investigated the effect of a simple quality improvement initiative on DNT for IVT. METHODS: This is a single-center study of patients treated with IVT between 2013 and 2017. A simple quality improvement initiative was implemented in January 2015 to allow the Stroke team to manage hypertension in the emergency room, to make decision for IVT before getting blood test results unless patients were taking oral anticoagulants, and to give IVT in the CT suite. Baseline characteristics, DNT and outcomes at hospital discharge were compared between pre- and post-intervention groups. RESULTS: Ninety and 136 patients were treated with IVT in pre- and post-intervention groups, respectively. The rate of IVT was significantly higher in the post-intervention group (20% vs. 14.4%, p = 0.007). The median DNT with interquartile range (IQR) was reduced significantly by 23 min (63[53-81] vs. 40[29-53], p < 0.001) with more patients in the post-intervention group receiving IVT within 60 min (81.6% vs. 46.7%) and 45 min (64.0% vs.17.8%). There was no significant difference in symptomatic intracerebral hemorrhage rate (1.5% vs. 1.1%), modified Rankin Scale 0-1 (29.4% vs. 23.3%), and hospital mortality (7.4% vs. 6.7%) between the 2 groups. CONCLUSIONS: Three easily-implementable quality improvement initiative increases IVT rate and reduces DNT significantly without increasing the rate of IVT-related complications in our comprehensive stroke center.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Fibrinolíticos/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/métodos , Administración Intravenosa , Anciano , Anciano de 80 o más Años , Hemorragia Cerebral/epidemiología , Servicio de Urgencia en Hospital , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Mejoramiento de la Calidad , Tiempo de Tratamiento
20.
Crit Rev Eukaryot Gene Expr ; 29(2): 105-112, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31679265

RESUMEN

OBJECTIVE: In this study, the molecular mechanism by which EPO regulates the angiogenesis after cerebral ischemia through AMPK-KLF2 signaling pathway was investigated. METHODS: Sixty healthy, male, C57BL/6 mice were randomly divided into three groups of 20 mice: a sham group, the middle cerebral artery occlusion (MCAO) group, and a MCAO+EPO treatment group. The MCAO model was established using a modified ZeaLonga method. Mice in the EPO treatment group were injected with EPO immediately after reperfusion (5000 IU/kg), and EPO was injected the following day. The number of mouse deaths and neurologic function scores were recorded during the experiment. On day 7 after cerebral ischemia, brain tissue proteins were extracted. The following proteins expressions were detected by western blot assay: EPO, vascular endothelial growth factor (VEGE), vascular endothelial growth factor receptor (KDR), adenosine activated protein kinase (AMPK), and alpha HIF-1α alpha (HIF-1α), KLF2 and nitric oxide synthase (eNOS). RESULTS: Compared with the MCAO group, the survival rate of mice in the EPO group was significantly improved and neurological function was significantly improved (P < 0.01). Western blot results showed that the content of EPO in brain tissue in MCAO group significantly increased compared with sham group. The content of EPO in the brain tissue of mice in the MCAO+EPO treatment group was significantly higher than in that of the MCAO group, which indicates that EPO increased the content of EPO in mouse brain tissue. Compared with the sham group, the protein expression of vascular endothelial growth factor (VEGE) and its receptor (KDR) in brain tissue of the MCAO group significantly decreased. However, the protein expression of VEGE and its receptor KDR in brain tissue of rats treated with MCAO+EPO was significantly higher than in that of the MCAO group. Thus, in this study, EPO was associated with vascular endothelial differentiation after cerebral ischemia in mice. The results of AMPK and KLF2 showed that the expression levels of AMPK and KLF2 in brain tissues of MCAO group mice significantly decreased compared with the sham group. However, the expression levels of AMPK and KLF2 in brain tissues of mice treated with MCAO+EPO were significantly higher than those in the MCAO group. Thus, EPO can activate AMPK and upregulate the expression of the transcription factor KLF2. The protein expression of HIF-1α in the brain tissue of mice in the MCAO group significantly increased compared with the sham group. However, the expression of HIF-1α in mice brain tissues in the MCAO+EPO treatment group was significantly lower than in that of the MCAO group, indicating that EPO was involved in regulating HIF-1α expression. The eNOS results showed that, compared with Sham group, the protein expression of eNOS in brain tissue of MCAO group mice significantly decreased. In the MCAO+EPO treatment group, the protein expression of eNOS was significantly higher in the brain tissue of the mice than in that of the MCAO group, indicating that EPO was involved in the synthesis of NO and promoted the angiogenesis. CONCLUSION: EPO promotes VEGE and its receptor (KDR) expression and participates in the regulation of HIF-1α and eNOS protein expression through the activation of AMPK-KLF2 signaling pathways to promote new vascular development after cerebral ischemia.


Asunto(s)
Isquemia Encefálica/fisiopatología , Encéfalo/irrigación sanguínea , Encéfalo/efectos de los fármacos , Eritropoyetina/farmacología , Neovascularización Patológica , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Moduladores de la Angiogénesis/farmacología , Moduladores de la Angiogénesis/uso terapéutico , Animales , Encéfalo/fisiopatología , Isquemia Encefálica/tratamiento farmacológico , Eritropoyetina/uso terapéutico , Regulación de la Expresión Génica/efectos de los fármacos , Factores de Transcripción de Tipo Kruppel/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Distribución Aleatoria
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