RESUMEN
CONTEXT: Lacunar strokes and diabetes are risk factors for cognitive dysfunction. Elucidating modifiable risk factors for cognitive dysfunction has great public health implications. One factor may be glycemic status, as measured by glycated hemoglobin (A1c). OBJECTIVE: The aim of this study was to assess the relationship between A1c and cognitive function in lacunar stroke patients with diabetes. METHODS: The effect of baseline and follow-up A1c on the baseline and the change in Cognitive Assessment Screening Instrument (CASI) score over time among participants with a median of 2 cognitive assessments (range, 1-5) was examined in 942 individuals with diabetes and a lacunar stroke who participated in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (ClinicalTrials.gov No. NCT00059306). RESULTS: Every 1% higher baseline A1c was associated with a 0.06 lower standardized CASI z score (95% CI, -0.101 to -0.018). Higher baseline A1c values were associated with lower CASI z scores over time (P for interactionâ =â .037). A 1% increase in A1c over time corresponded with a CASI score decrease of 0.021 (95% CI, -0.0043 to -0.038) during follow-up. All these remained statistically significant after adjustment for age, sex, education, race, depression, hypertension, hyperlipidemia, body mass index, cardiovascular disease, obstructive sleep apnea, diabetic retinopathy, nephropathy insulin use, and white-matter abnormalities. CONCLUSION: This analysis of lacunar stroke patients with diabetes demonstrates a relationship between A1c and change in cognitive scores over time. Intervention studies are needed to delineate whether better glucose control could slow the rate of cognitive decline in this high-risk population.
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Cognición , Diabetes Mellitus/metabolismo , Diabetes Mellitus/psicología , Glucosa/metabolismo , Accidente Vascular Cerebral Lacunar/metabolismo , Accidente Vascular Cerebral Lacunar/psicología , Anciano , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Accidente Vascular Cerebral Lacunar/complicacionesRESUMEN
Immune-inflammatory, metabolic, oxidative, and nitrosative stress (IMO&NS) pathways and, consequently, neurotoxicity are involved in acute ischemic stroke (IS). The simultaneous assessment of multiple IMO&NS biomarkers may be useful to predict IS and its prognosis. The aim of this study was to identify the IMO&NS biomarkers, which predict short-term IS outcome. The study included 176 IS patients and 176 healthy controls. Modified Rankin scale (mRS) was applied within 8 h after IS (baseline) and 3 months later (endpoint). Blood samples were obtained within 24 h after hospital admission. IS was associated with increased white blood cell (WBC) counts, high sensitivity C-reactive protein (hsCRP), interleukin (IL-6), lipid hydroperoxides (LOOHs), nitric oxide metabolites (NOx), homocysteine, ferritin, erythrocyte sedimentation rate (ESR), glucose, insulin, and lowered iron, 25-hydroxyvitamin D [25(OH)D], total cholesterol, and high-density lipoprotein (HDL) cholesterol. We found that 89.4% of the IS patients may be correctly classified using the cumulative effects of male sex, systolic blood pressure (SBP), glucose, NOx, LOOH, 25(OH)D, IL-6, and WBC with sensitivity of 86.2% and specificity of 93.0%. Moreover, increased baseline disability (mRS ≥ 3) was associated with increased ferritin, IL-6, hsCRP, WBC, ESR, and glucose. We found that 25.0% of the variance in the 3-month endpoint (mRS) was explained by the regression on glucose, ESR, age (all positively), and HDL-cholesterol, and 25(OH)D (both negatively). These results show that the cumulative effects of IMO&NS biomarkers are associated with IS and predict a poor outcome at 3-month follow-up.
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Accidente Cerebrovascular Embólico/metabolismo , Inflamación/metabolismo , Arteriosclerosis Intracraneal/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Estrés Fisiológico/fisiología , Accidente Vascular Cerebral Lacunar/metabolismo , Anciano , Biomarcadores/metabolismo , Glucemia/metabolismo , Sedimentación Sanguínea , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Colesterol/metabolismo , HDL-Colesterol/metabolismo , Accidente Cerebrovascular Embólico/fisiopatología , Femenino , Ferritinas/metabolismo , Homocisteína/metabolismo , Humanos , Insulina/metabolismo , Interleucina-6/metabolismo , Arteriosclerosis Intracraneal/fisiopatología , Accidente Cerebrovascular Isquémico/fisiopatología , Recuento de Leucocitos , Peróxidos Lipídicos/metabolismo , Masculino , Persona de Mediana Edad , Nitratos/metabolismo , Nitritos/metabolismo , Estrés Nitrosativo/fisiología , Estrés Oxidativo/fisiología , Accidente Vascular Cerebral Lacunar/fisiopatología , Vitamina D/análogos & derivados , Vitamina D/metabolismoRESUMEN
BACKGROUND: Vascular calcification is one of the mechanisms underlying the pathogenesis of cerebral small vessel disease (CSVD). Whether higher levels of serum alkaline phosphatase (ALP), a predictor of vascular calcification, are independently associated with CSVD remains inconclusive. PURPOSE: The present study explored the link between levels of circulating ALP and CSVD in a Chinese population. METHODS: A total of 568 participants were recruited from the healthcare center at the affiliated Zhongshan Hospital of Dalian University and the Fifth People Hospital of Dalian between January 2010 and December 2016. The subjects were divided into three groups based on the infarct and severity of white matter hyper-intensities (WMH) as categorized by brain magnetic resonance imaging (MRI) analysis and Fazekas rating scales: no/mild cerebral WMH (nm-WMH); moderate-to-severe WMH (MS-WMH); and silent lacunar infarct (SLI). The subjects were also divided into three tertiles based on circulating levels of ALP: ≤64, 65-105 and ≥106 (IU/L). Information regarding the risk factors, such as coronary artery disease, diabetes mellitus, hypertension and serum ALP level, C-reactive protein, homocysteine (HCY), and other laboratory results, were collected. The associations of ALP with WMH and SLI were evaluated using logistic regression analysis. RESULTS: After adjustment for vascular risk factors, subjects with MS-WMH and SLI were more likely to have ALP levels ≥106 IU/L than ≤64 IU/L. The mean circulating level of ALP was substantially increased in patients with MS-WMH or SLI compared with patients with nm-WMH. The multivariate model revealed that this significant difference remained when MS-WMH or SLI was added to the model, after adjustment for confounding factors. CONCLUSION: The circulating level of ALP was positively correlated with a high risk of silent lacunar infarct and white matter hyperintensity; important indicators of small vessel disease.
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Fosfatasa Alcalina/metabolismo , Enfermedades de los Pequeños Vasos Cerebrales/metabolismo , Accidente Vascular Cerebral Lacunar/metabolismo , Fosfatasa Alcalina/genética , Enfermedades de los Pequeños Vasos Cerebrales/genética , Femenino , Humanos , Hipertensión/genética , Hipertensión/metabolismo , Incidencia , Masculino , Factores de Riesgo , Accidente Vascular Cerebral Lacunar/genéticaRESUMEN
BACKGROUND The aim of this study was to investigate the correlations of C-reactive protein (CRP), interleukin-6 (IL-6), and insulin resistance (IR) with cerebral infarction in hypertensive patients. MATERIAL AND METHODS A total of 80 patients with cerebral infarction admitted to our hospital from March 2016 to November 2017 were selected and divided into 2 groups according to the diameter of cerebral infarction, namely, lacunar cerebral infarction group (n=40) and cerebral infarction group (n=40). The levels of high-sensitivity CRP (hs-CRP) and IL-6, homeostasis model assessment of IR (HOMA-IR) index and blood pressure level were compared between the 2 groups. The correlations of hs-CRP level, IL-6 level, and IR with the diameter of cerebral infarction, as well as the relationships of hs-CRP level and IR with the neurological function score after cerebral infarction were analyzed. RESULTS The levels of hs-CRP and IL-6 in the cerebral infarction group were significantly higher than those in the lacunar cerebral infarction group (P<0.05). The cerebral infarction group had a markedly higher HOMA-IR index than the lacunar cerebral infarction group (P<0.05), but it had remarkably decreased systolic blood pressure and diastolic blood pressure compared with those in the lacunar cerebral infarction group (P<0.05). There were positive correlations of hs-CRP level, IL-6 level, and IR with the diameter of cerebral infarction (P<0.05). The hs-CRP level and IR had positive correlations with the neurological function score after cerebral infarction (P<0.05). CONCLUSIONS In hypertensive patients complicated with cerebral infarction, the body's inflammatory factors, and IR are positively correlated with the diameter of cerebral infarction, as well as the neurological prognosis of the patients.
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Infarto Cerebral/metabolismo , Hipertensión/complicaciones , Accidente Vascular Cerebral Lacunar/metabolismo , Anciano , Anciano de 80 o más Años , Glucemia , Presión Sanguínea , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Infarto Cerebral/fisiopatología , Femenino , Humanos , Resistencia a la Insulina/fisiología , Interleucina-6/análisis , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Accidente Vascular Cerebral Lacunar/fisiopatologíaRESUMEN
We use the modified pial vessel disruption rat model to elucidate the cellular and molecular mechanisms of cavitation as it plays a role in lacunar infarction. Here we discuss the similarities between the genesis of pulmonary cavitation in various animal models and lacunar infarction in the cerebral cortex of rats. Both pathological processes involve the creation of a cavity surrounded by fibroblasts or reactive astrocytes. A crucial step in both, the lung and the cerebral cortex, appears to be the migration of neutrophils across the endothelial barrier into the parenchyma. In the lung and cerebral cortex this involves release of matrix metalloproteinase-9 (MMP-9). Inside the parenchyma neutrophils continue to release MMP-9. In both situations batimastat (BB-94) and minocycline reduce release of MMP-9 and prevent cavitation. In the cerebral cortex MMP-9 release by resident microglia plays an additional role. We therefore advance the hypothesis that cavitation in both tissues is driven by MMP-9 originating from invading neutrophils. Therapeutic intervention has to focus on these blood-borne intruder cells and specific MMP actions. Batimastat and its derivatives (marimastat, BB-1101, mCGS-27023-A, ilomastat, GM6001, CTK8G1150) are already in clinical or experimental use in humans for anti-cancer treatment, and these clinically relevant drugs could be repurposed to act as anti-inflammatory to counter neutrophil contribution to lung or cerebral cortex cavitation.
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Metaloproteinasa 9 de la Matriz/biosíntesis , Infiltración Neutrófila/fisiología , Accidente Vascular Cerebral Lacunar/metabolismo , Animales , Humanos , Fenilalanina/análogos & derivados , Fenilalanina/farmacología , Inhibidores de Proteasas/farmacología , Ratas , Accidente Vascular Cerebral Lacunar/patología , Tiofenos/farmacologíaRESUMEN
SEE COHEN DOI101093/AWW183 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Amyloid-ß and cerebral small vessel disease are the two major causes of cognitive impairment in the elderly. However, the underlying mechanisms responsible for precisely how amyloid-ß and cerebral small vessel disease affect cognitive impairment remain unclear. We investigated the effects of amyloid-ß and lacunes on downstream imaging markers including structural network and cortical thickness, further analysing their relative impact on cognitive trajectories. We prospectively recruited a pool of 117 mild cognitive impairment patients (45 amnestic type and 72 subcortical vascular type), from which 83 patients received annual follow-up with neuropsychological tests and brain magnetic resonance imaging for 3 years, and 87 patients received a second Pittsburgh compound B positron emission tomography analysis. Structural networks based on diffusion tensor imaging and cortical thickness were analysed. We used linear mixed effect regression models to evaluate the effects of imaging markers on cognitive decline. Time-varying Pittsburgh compound B uptake was associated with temporoparietal thinning, which correlated with memory decline (verbal memory test, unstandardized ß = -0.79, P < 0.001; visual memory test, unstandardized ß = -2.84, P = 0.009). Time-varying lacune number was associated with the degree of frontoparietal network disruption or thinning, which further affected frontal-executive function decline (Digit span backward test, unstandardized ß = -0.05, P = 0.002; Stroop colour test, unstandardized ß = -0.94, P = 0.008). Of the multiple imaging markers analysed, Pittsburgh compound B uptake and the number of lacunes had the greatest association with memory decline and frontal-executive function decline, respectively: Time-varying Pittsburgh compound B uptake (standardized ß = -0.25, P = 0.010) showed the strongest effect on visual memory test, followed by time-varying temporoparietal thickness (standardized ß = 0.21, P = 0.010) and time-varying nodal efficiency (standardized ß = 0.17, P = 0.024). Time-varying lacune number (standardized ß = -0.25, P = 0.014) showed the strongest effect on time-varying digit span backward test followed by time-varying nodal efficiency (standardized ß = 0.17, P = 0.021). Finally, time-varying lacune number (ß = -0.22, P = 0.034) showed the strongest effect on time-varying Stroop colour test followed by time-varying frontal thickness (standardized ß = 0.19, P = 0.026). Our multimodal imaging analyses suggest that cognitive trajectories related to amyloid-ß and lacunes have distinct paths, and that amyloid-ß or lacunes have greatest impact on cognitive decline. Our results provide rationale for the targeting of amyloid-ß and lacunes in therapeutic strategies aimed at ameliorating cognitive decline.
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Péptidos beta-Amiloides/metabolismo , Compuestos de Anilina , Corteza Cerebral , Enfermedades de los Pequeños Vasos Cerebrales , Disfunción Cognitiva , Función Ejecutiva/fisiología , Imagen por Resonancia Magnética/métodos , Trastornos de la Memoria , Tomografía de Emisión de Positrones/métodos , Tiazoles , Anciano , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/metabolismo , Corteza Cerebral/fisiopatología , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/metabolismo , Enfermedades de los Pequeños Vasos Cerebrales/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/fisiopatología , Femenino , Humanos , Estudios Longitudinales , Masculino , Trastornos de la Memoria/diagnóstico por imagen , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/fisiopatología , Accidente Vascular Cerebral Lacunar/diagnóstico por imagen , Accidente Vascular Cerebral Lacunar/metabolismo , Accidente Vascular Cerebral Lacunar/fisiopatologíaRESUMEN
BACKGROUND: Stroke is the second most common cause of mortality in China. Although most subtypes of ischemic stroke share similar risk factors, they have different etiologies. Our study aimed to evaluate the different risk factor profiles between the stroke subtypes, lacunar infarcts (LI) and large-artery atherosclerosis (LAA), and clarify the characteristics of current acute ischemic stroke in China. METHODS: In this cross-sectional study, we analyzed the clinical characteristics of 1982 patients with acute ischemic stroke who were admitted to the neurology department at the Peking University First Hospital between 2007 and 2014. Ischemic stroke was further classified into LAA, LI, cardioembolism (CE) and undetermined causes of infarction (UDI) according to TOAST classification. Demographic characteristics, risk factors, as well as the findings of laboratory and imaging tests of 1773 patients with LAA and LI, were analyzed by univariate and multivariate logistic analysis. RESULTS: Of the 1982 ischemic stroke patients included in this study, 1207 were diagnosed with LAA, 566 with LI, 173 with cardioembolism (CE) and 36 with undetermined causes of infarction (UDI). By comparing the risk factors in multivariate logistic regression analysis, hypertension [odds ratio (OR) = 1.832] and white matter leukoaraiosis (WML) (OR = 1.865) were found to be more strongly correlated with LI than LAA. Low density lipoprotein- cholesterol (LDL-c) (OR = 0.774) were more strongly related to LAA than LI. CONCLUSIONS: This study found that hypertension and WML were more strongly correlated with LI than LAA. LDL-c was more strongly related to LAA than LI.
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Arterias/patología , Aterosclerosis/complicaciones , Accidente Vascular Cerebral Lacunar/etiología , Anciano , Arterias/metabolismo , Aterosclerosis/metabolismo , Isquemia Encefálica/complicaciones , Isquemia Encefálica/metabolismo , China , LDL-Colesterol/metabolismo , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Accidente Vascular Cerebral Lacunar/metabolismoRESUMEN
BACKGROUND: Cerebral microvascular abnormality is frequently associated with lacunar and subcortical ischemic lesions. We performed acute and follow-up CT perfusion scans over the first 3 months after ischemic stroke to investigate disturbances of the blood-brain barrier (BBB) and cerebral perfusion in patients with lacunar/subcortical lesions compared to those with cortical lesions alone. METHODS: Thirty-one patients with lacunar/subcortical infarct (n = 14) or with cortical large vessel infarct (n = 17) were recruited and underwent a CT perfusion study at admission, 24 h, 7 days and 3 months after stroke using a two-phase imaging protocol. Functional maps of BBB permeability surface area product (BBB-PS), cerebral blood flow (CBF) and blood volume (CBV) at follow-up were co-registered with those at admission, and the measurements in non-infarcted ipsilateral basal ganglia and thalamus were compared within each group and between the two groups. RESULTS: For the lacunar/subcortical group, BBB-PS within non-infarcted ipsilateral basal ganglia and thalamus peaked at day 7 compared to all other time points, and was significantly higher than the cortical group at day 7 and month 3. The CBF and CBV in the same region were significantly lower at admission and transient hyperemia was seen at day 7 in the lacunar/subcortical group. CONCLUSION: Disturbed BBB-PS and compromised cerebral perfusion over the first 3 months post stroke were shown in the non-infarcted basal ganglia and thalamus of lacunar/subcortical stroke using CT perfusion. Future studies are required to elucidate the relationship of post-stroke BBB disturbances to chronic cognitive impairment.
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Ganglios Basales/irrigación sanguínea , Barrera Hematoencefálica/metabolismo , Circulación Cerebrovascular , Accidente Vascular Cerebral Lacunar/metabolismo , Tálamo/irrigación sanguínea , Anciano , Anciano de 80 o más Años , Ganglios Basales/metabolismo , Permeabilidad Capilar , Estudios de Casos y Controles , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Imagen de Perfusión , Permeabilidad , Estudios Prospectivos , Accidente Cerebrovascular/metabolismo , Tálamo/metabolismo , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND AND PURPOSE: The relationship between chronic kidney disease and cerebral small vessel disease (cSVD), especially enlarged perivascular spaces (EPVS), has not been fully understood. This study aimed to investigate the association of chronic kidney disease and EPVS, as well as the total burden of cSVD on magnetic resonance imaging, expressed by the simultaneous presence of multiple markers of cSVD, among patients with first-ever lacunar stroke. METHODS: Four hundred and thirteen consecutive patients were prospectively enrolled. Centrum semiovale and basal ganglia EPVS on T2-weighted magnetic resonance imaging, as well as other imaging markers of cSVD, including lacune, white matter lesions, and cerebral microbleeds, were rated using validated scales. Chronic kidney disease was defined as either reduced estimated glomerular filtration rate or the presence of proteinuria. RESULTS: After adjustments for potential confounders by logistic regression, proteinuria and impaired estimated glomerular filtration rate were correlated with the severity of EPVS in both centrum semiovale (odds ratio [OR] 2.59; 95% confidence interval [CI] 1.19-5.64 and OR 2.37; 95% CI 1.19-4.73) and basal ganglia (OR 5.12; 95% CI 2.70-12.10 and OR 4.17; 95% CI 2.08-8.37). A similar association was also found between proteinuria and low estimated glomerular filtration rate levels and the comprehensive cSVD burden (OR 2.13; 95% CI 1.10-4.14 and OR 5.59; 95% CI 2.58-12.08). CONCLUSIONS: Proteinuria and impaired estimated glomerular filtration rate are associated with increasing EPVS severity and, furthermore, accumulated magnetic resonance imaging burden of cSVD in patients with first-ever acute lacunar stroke.
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Ganglios Basales/patología , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico , Imagen por Resonancia Magnética , Insuficiencia Renal Crónica/diagnóstico , Accidente Vascular Cerebral Lacunar/diagnóstico , Anciano , Ganglios Basales/metabolismo , Enfermedades de los Pequeños Vasos Cerebrales/epidemiología , Enfermedades de los Pequeños Vasos Cerebrales/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/metabolismo , Accidente Vascular Cerebral Lacunar/epidemiología , Accidente Vascular Cerebral Lacunar/metabolismoRESUMEN
Ambulatory arterial stiffness index (AASI) is associated with microvascular damage in other organs, but the association with microvascular brain damage is unknown. The association of AASI with magnetic resonance imaging (MRI) markers of cerebral small vessel disease in 143 patients with lacunar stroke was investigated. We performed 24-hour ambulatory blood pressure monitoring and scored the presence of lacunes, white matter hyperintensities, perivascular spaces, and cerebral microbleeds on brain MRI. In logistic regression analyses, AASI was associated with white matter hyperintensities, but, after adjustment for age and sex, this association lost significance. AASI was not associated with lacunes, microbleeds, or perivascular spaces. Systolic and diastolic 24-hour blood pressure values were associated with lacunes, perivascular spaces, and microbleeds independent of age and sex. Despite its significance and growing interest as a possible prognostic and therapeutic target in (micro)vascular diseases, AASI seems to have no added value over standard 24-hour blood pressure in cerebral small vessel disease.
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Imagen por Resonancia Magnética/métodos , Accidente Vascular Cerebral Lacunar/patología , Rigidez Vascular/fisiología , Anciano , Monitoreo Ambulatorio de la Presión Arterial/métodos , Femenino , Humanos , Hipertensión/patología , Hipertensión/fisiopatología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Monitoreo Ambulatorio/métodos , Estudios Prospectivos , Análisis de la Onda del Pulso/métodos , Factores de Riesgo , Accidente Vascular Cerebral Lacunar/diagnóstico , Accidente Vascular Cerebral Lacunar/metabolismoRESUMEN
BACKGROUND: Lacunar infarction (LACI) is a subtype of acute ischemic stroke affecting around 25% of all ischemic stroke cases. Despite having an excellent recovery during acute phase, certain LACI patients have poor mid- to long-term prognosis due to the recurrence of vascular events or a decline in cognitive functions. Hence, blood-based biomarkers could be complementary prognostic and research tools. METHODS AND FINDING: Plasma was collected from forty five patients following a non-disabling LACI along with seventeen matched control subjects. The LACI patients were monitored prospectively for up to five years for the occurrence of adverse outcomes and grouped accordingly (i.e., LACI-no adverse outcome, LACI-recurrent vascular event, and LACI-cognitive decline without any recurrence of vascular events). Microvesicles-enriched fractions isolated from the pooled plasma of four groups were profiled by an iTRAQ-guided discovery approach to quantify the differential proteome. The data have been deposited to the ProteomeXchange with identifier PXD000748. Bioinformatics analysis and data mining revealed up-regulation of brain-specific proteins including myelin basic protein, proteins of coagulation cascade (e.g., fibrinogen alpha chain, fibrinogen beta chain) and focal adhesion (e.g., integrin alpha-IIb, talin-1, and filamin-A) while albumin was down-regulated in both groups of patients with adverse outcome. CONCLUSION: This data set may offer important insight into the mechanisms of poor prognosis and provide candidate prognostic biomarkers for validation on larger cohort of individual LACI patients.
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Biomarcadores/sangre , Micropartículas Derivadas de Células/metabolismo , Proteómica/métodos , Accidente Vascular Cerebral Lacunar/sangre , Accidente Vascular Cerebral Lacunar/diagnóstico , Anciano , Coagulación Sanguínea , Cromatografía , Análisis por Conglomerados , Demografía , Femenino , Adhesiones Focales/metabolismo , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Marcaje Isotópico , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Pronóstico , Proteoma/metabolismo , Electricidad Estática , Accidente Vascular Cerebral Lacunar/metabolismoRESUMEN
OBJECTIVE: Increasing blood pressure (BP) variability is reported to be a cardiovascular risk factor. However, the clinical implications of postprandial hypotension (PHYPO), a commonly observed BP variability in elderly persons, are poorly understood. Here, we investigated the possible associations between postprandial BP decline and asymptomatic cerebral damage in community residents. METHODS: Study participants consisted of 1308 general community residents (65â±â9 years old). Postprandial BP change was calculated from SBP measured just before and 30âmin after lunch. PHYPO was defined as a decline in SBP of more than 20âmmHg. The presence of asymptomatic cerebrovascular damage was evaluated by brain MRI. RESULTS: Prevalence of lacunar infarction was significantly higher in participants with PHYPO (Pâ=â0.004). A postprandial decline in SBP was linearly increased with the number of lacunar lesions (none, nâ=â1200, -3.4±â11.3âmmHg; one lesion, nâ=â82, -5.2â±â11.8; two lesions, nâ=â18, -6.9â±â11.5; three lesions, nâ=â7, -13.4â±â11.3; and four lesions, nâ=â1, -27; Pâ=â0.012). Although participants with PHYPO were older (Pâ<â0.001) and had higher preprandial BP (Pâ<â0.001) and faster pulse wave velocity (Pâ=â0.001), multivariate analysis adjusted for these covariates indicated that postprandial BP decline was an independent determinant for the number of lacunar infarctions (Pâ=â0.004). No significant associations were observed with grade of periventricular hyperintensity or frequency of microbleeds. These relationships were also found in an analysis based on central BP, whereas no superiority was seen in the analysis based on central BP. CONCLUSION: Postprandial BP decline is an overlooked risk marker for asymptomatic lacunar infarction in community residents.
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Biomarcadores/metabolismo , Hipotensión/epidemiología , Periodo Posprandial , Accidente Vascular Cerebral Lacunar/metabolismo , Anciano , Presión Sanguínea , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Neuroinflammation is believed to be involved in the pathophysiological mechanisms of silent brain infarcts (SBI). However, the immunological profile of SBI has been scarcely investigated. In the context of a national research project named SILENCE, aimed at investigating clinical, biochemical and pathogenic features of SBI, we have measured the plasma profile of some inflammatory-related molecules in SBI patients (nâ=â21), patients with recent lacunar infarcts (LI, nâ=â28) and healthy controls (nâ=â31), consecutively enrolled in four Italian centres. A panel of chemokines (MIG, CTACK, IL16, SDF1a, MCP1), growth factors (SCF, SCGFb, HGF, IL3), immunoglobulin-type adhesion molecules (ICAM1, VCAM1), proinflammatory cytokines (IL18, INFa2, MIF, IL12p40), cell surface receptors on T-cells (IL2Ra), and inductors of apoptosis (TRAIL) was assessed in plasma samples by Luminex xMAP™ technology. Immunological parameters were compared using non-parametric statistics and performance to distinguish SBI and LI was evaluated by receiver operating characteristic (ROC) analysis. Plasma levels of ICAM1 were significantly higher in both SBI and LI patients as compared to controls (SBI≥LI>Ctrl). A different trend was observed for IL16 (SBI
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Infarto Encefálico/inmunología , Infarto Encefálico/metabolismo , Accidente Vascular Cerebral Lacunar/inmunología , Accidente Vascular Cerebral Lacunar/metabolismo , Anciano , Biomarcadores , Infarto Encefálico/etiología , Moléculas de Adhesión Celular/sangre , Quimiocinas/sangre , Citocinas/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Receptores de Superficie Celular/metabolismo , Factores de Riesgo , Accidente Vascular Cerebral Lacunar/etiologíaRESUMEN
BACKGROUND AND PURPOSE: Definitions for chronic lacunar infarcts vary. Recent retrospective studies suggest that many acute lacunar strokes do not develop a cavitated appearance. We determined the characteristics of acute lacunar infarcts on follow-up MRI in consecutive patients participating in prospective research studies. METHODS: Patients with acute lacunar infarction on diffusion-weighted imaging were selected from 3 prospective cohort studies of minor stroke imaged within <24 hours of onset. Follow-up MRI was performed at 30 days (Vascular Imaging of Acute Stroke for Identifying Predictors of Clinical Outcome and Recurrent Ischemic Events [VISION] study, n=21) or 90 days (VISION-2 and CT and MRI in the Triage of TIA and Minor Cerebrovascular Events to Identify High Risk Patients [CATCH] studies, n=34). Evidence of cavitation on MRI was rated separately on fluid-attenuated inversion recovery, T1, and T2 sequences by 2 independent study physicians; discrepant readings were resolved by consensus. RESULTS: Probable or definite cavitation on any sequence was more common at 90 days compared with 30 days (P≤0.001 for all sequences). At 90 days, evidence of cavitation was seen on at least 1 sequence in 33 of 34 patients (97%). The T1-weighted sequence was most sensitive to the presence of cavitation (94% at 90 days). By contrast, the fluid-attenuated inversion recovery sequence frequently failed to show evidence of cavitation in the brain stem or thalamus (only 10 of 18 [56%] showed cavitation). CONCLUSIONS: MRI scanning at 90 days with T1-weighted imaging reveals evidence of cavitation in nearly all cases of acute lacunar infarction. By contrast, reliance on fluid-attenuated inversion recovery alone will miss many cavitated lesions in the thalamus and brain stem. These factors should be taken into account in the development of standardized criteria for lacunar infarction on MRI.
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Imagen de Difusión por Resonancia Magnética/métodos , Accidente Vascular Cerebral Lacunar/diagnóstico , Accidente Vascular Cerebral Lacunar/metabolismo , Enfermedad Aguda , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de TiempoRESUMEN
OBJECTIVES: New insights in the pathophysiology of lacunar stroke (LS) suggest that it is caused by increased permeability of the blood-brain barrier due to endothelial activation. Because endothelial cells are the major production and storage site of tissue factor pathway inhibitor (TFPI), this protein can be used as marker of endothelial activation. In this observational study we measured the different pools of TFPI, as a marker of endothelial function, in first-ever lacunar stroke patients. METHODS: We determined antigen levels of total and free full-length (FL) TFPI using ELISA in 149 patients and 42 controls. Heparin-releasable free FL TFPI was determined in a random subset of 17 patients and 15 controls. By brain MRI, we classified LS patients as having isolated lacunar infarct (ILA) or silent ischemic lesions (SILs). RESULTS: Plasma levels of total TFPI were highest in patients with SILs compared with those with ILA, but this association disappeared after correction for age and levels of low-density lipoprotein cholesterol. However, levels of heparin-releasable free FL TFPI were higher in patients than in controls. CONCLUSIONS: Although ambient plasma levels of total TFPI were not different in subtypes of LS, the increased levels of heparin-releasable TFPI in patients suggest a role of endothelial activation in the pathogenesis of LS.
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Anticoagulantes/farmacología , Heparina/farmacología , Lipoproteínas/metabolismo , Accidente Vascular Cerebral Lacunar/metabolismo , Factores de Edad , Anciano , Biomarcadores , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Protocolos Clínicos , Dinamarca , Endotelio Vascular/fisiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos Logísticos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros , Factores de Riesgo , Accidente Vascular Cerebral Lacunar/clasificaciónRESUMEN
Limited evidence exists on the relationships between severity of white-matter lesions (WMLs) and cerebral hemodynamics in patients without major cerebral artery disease. To examine changes of cerebral blood flow (CBF), oxygen metabolism, and vascular reserve capacity associated with severity of WML in patients with lacunar stroke, we used a positron emission tomography (PET). Eighteen lacunar patients were divided into two groups according to the severity of WMLs, assessed by Fazekas classification; grades 0 to 1 as mild WML group and grades 2 to 3 as severe WML group. Rapid dual autoradiography was performed with (15)O-labeled gas-PET followed by (15)O-labeled water-PET with acetazolamide (ACZ) challenge. Compared with the mild WML group, the severe WML group showed lower CBF (20.6±4.4 versus 29.9±8.2 mL/100 g per minute, P=0.008), higher oxygen extraction fraction (OEF) (55.2±7.4 versus 46.7±5.3%, P=0.013), and lower cerebral metabolic rate of oxygen (CMRO(2)) (1.95±0.41 versus 2.44±0.42 mL/100 g per minute, P=0.025) in the centrum semiovale. There were no significant differences in the ACZ reactivity between the two groups (48.6±22.6% versus 42.5±17.2%, P=0.524). Lacunar patients with severe WMLs exhibited reduced CBF and CMRO(2), and increased OEF in the centrum semiovale. The ACZ reactivity was preserved in both patients with severe and mild WMLs in each site of the brain.
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Cerebelo/diagnóstico por imagen , Cerebelo/metabolismo , Glicina/análogos & derivados , Tomografía de Emisión de Positrones , Accidente Vascular Cerebral Lacunar/diagnóstico por imagen , Accidente Vascular Cerebral Lacunar/metabolismo , Anciano , Cerebelo/irrigación sanguínea , Circulación Cerebrovascular/efectos de los fármacos , Femenino , Glicina/farmacología , Humanos , Masculino , RadiografíaRESUMEN
OBJECTIVES: Fat tissue is an important endocrine organ that produces a number of hormones and cytokines (leptin, adiponectin, resistin, plasminogen activator inhibitor-1, Tumour necrosis factor TNF α) with essential roles in regulation of many physiological functions. METHODS: We targeted implications of adipokines in ischemic stroke patients. Patients with acute stroke were examined (n=145) and the results were compared with the control group (n=68). We have examined potential associations between leptin, adiponectin and ghrelin, and different types of stroke and traditional risk factors. RESULTS: Significantly higher levels of leptin and lower levels of adiponectin and ghrelin were confirmed in the stroke group. The level of leptin in women with stroke was three-times higher than in men, and the leptin levels positively correlated with obesity in both sexes. Ghrelin levels correlated mildly with triglyceride levels, and were dominant in men with cardioembolic stroke. Adiponectin levels were not different between men and women with acute stroke, and correlated with atherothrombotic and lacunar stroke types in men. CONCLUSIONS: Adipokines and ghrelin play an important role in ischemic stroke, but their function in stroke subtypes seems to be different and sex influenced. More research is required to confirm our results.