Sang-Bae Ko

Significant association of metabolic syndrome with silent brain infarction in elderly people

A silent brain infarction (SBI) can predict clinical overt stroke or dementia. Studies focusing on the elderly population, where SBI is most common, are sparse. We examined the associations between SBI and metabolic syndrome (MetS) in healthy elderly individuals. Neurologically healthy subjects (1,254 persons, 723 males) aged ≥65xa0years who underwent brain MRI were evaluated. MetS was diagnosed following the AHA/NHLBI-2005 criteria. We examined associations between full syndrome (at least three of the five conditions) as well as its components and SBI while controlling for possible confounders. One hundred and ninety-seven subjects (15.7%) were found to have one or more SBIs on MRI. Age (1-year difference) was found to be significantly related to SBI prevalence (OR 1.09; 95% CI 1.05–1.12). MetS was significantly associated with SBI (OR 1.68; 95% CI 1.15–2.44). The component model of MetS showed a strong significance between elevated blood pressure (OR 1.89; 95% CI 1.23–2.91) and SBI. Subjects exhibiting more components of MetS showed more prevalent SBI and multiple SBIs. MetS was found to be significantly associated with SBI in neurologically healthy elderly people. The positive trend between the number of MetS components and SBI could be used as a diagnostic tool to predict and prevent future stroke.

Cystatin C, a novel indicator of renal function, reflects severity of cerebral microbleeds

BackgroundChronic renal insufficiency, diagnosed using creatinine based estimated glomerular filtration rate (GFR) or microalbumiuria, has been associated with the presence of cerebral microbleeds (CMBs). Cystatin C has been shown to be a more sensitive renal indicator than conventional renal markers. Under the assumption that similar pathologic mechanisms of the small vessel exist in the brain and kidney, we hypothesized that the levels of cystatin C may delineate the relationship between CMBs and renal insufficiency by detecting subclinical kidney dysfunction, which may be underestimated by other indicators, and thus reflect the severity of CMBs more accurately.MethodsData was prospectively collected for 683 patients with ischemic stroke. The severity of CMBs was categorized by the number of lesions. Patients were divided into quartiles of cystatin C, estimated GFR and microalbumin/creatinine ratios. Ordinal logistic regression analysis was used to examine the association of each renal indicator with CMBs.ResultsIn models including both quartiles of cystatin C and estimated GFR, only cystatin C quartiles were significant (the highest vs. the lowest, adjusted OR, 1.88; 95% CI 1.05-3.38; p = 0.03) in contrast to estimated GFR (the highest vs. the lowest, adjusted OR, 1.28; 95% CI 0.38-4.36; p = 0.70). A model including both quartiles of cystatin C and microalbumin/creatinine ratio also showed that only cystatin C quartiles was associated with CMBs (the highest vs. the lowest, adjusted OR, 2.06; 95% CI 1.07-3.94; p = 0.03). These associations were also observed in the logistic models using log transformed-cystatin C, albumin/creatinine ratio and estimated GFR as continuous variables. Cystatin C was a significant indicator of deep or infratenorial CMBs, but not strictly lobar CMBs. In addition, cystatin C showed the greatest significance in c-statistics for the presence of CMBs (AUC = 0.73 ± 0.03; 95% CI 0.66-0.76; p = 0.02).ConclusionCystatin C may be the most sensitive indicator of CMB severity among the renal disease markers.

Anti-inflammatory effects of fimasartan via Akt, ERK, and NFκB pathways on astrocytes stimulated by hemolysate.

ObjectiveThe aim of this study was to investigate whether fimasartan, a novel angiotensin II receptor blocker, modulates hemolysate-induced inflammation in astrocytes.MethodsWe stimulated astrocytes with hemolysate to induce hemorrhagic inflammation in vitro. Astrocytes were pretreated with fimasartan and then incubated with hemolysate at different durations. Anti-inflammatory cell signaling molecules including Akt, extracellular signal regulated kinase (ERK), NFκB and cyclooxygenase-2 (COX-2) were assessed by western blotting. Pro-inflammatory mediators were evaluated by real-time RT-PCR and ELISA.ResultsThe stimulation by hemolysate generated a robust activation of inflammatory signaling pathways in astrocytes. Hemolysate increased the phosphorylation of Akt at 1xa0h, and ERK1/2 at 20xa0min compared with the control group and promoted the degradation of IκBα. Pretreated fimasartan significantly decreased hemolysate-induced phosphorylation of Akt and ERK1/2. In addition, fimasartan also suppressed NFκB-related inflammatory pathways induced by hemolysate, including reduction of the gene expression of NFκB, and decreased nuclear translocation of NFκB and degradation of IκB. This reduction of inflammatory upstream pathways decreased the expression of inflammatory end-products: COX-2 and interleukin-1 (IL-1β). Furthermore, the expression of COX-2 was attenuated by both Akt inhibitor (LY294002) and ERK inhibitor (U0126), and IκBα degradation was suppressed by LY294002.ConclusionsThese results demonstrate that pretreatment with fimasartan to astrocytes suppresses the inflammatory responses induced by hemolysate. Akt, ERK and NFκB were associated with hemolysate-induced COX-2 and IL-1β expression. Based on these mechanisms, fimasartan could be a candidate anti-inflammatory regulator for the treatment of intracerebral hemorrhage.

D‐dimer as a predictor of early neurologic deterioration in cryptogenic stroke with active cancer

The occurrence of stroke in cancer patients is caused by conventional vascular risk factors and cancer‐specific mechanisms. However, cryptogenic stroke in patients with cancer was considered to be more related to cancer‐specific hypercoagulability. In this study, we investigated the potential of the D‐dimer level to serve as a predictor of early neurologic deterioration (END) in cryptogenic stroke patients with active cancer.

Prolonged sleep increases the risk of intracerebral haemorrhage: a nationwide case−control study

Although abnormal sleep duration is positively associated with increased risk for cardiovascular disease and mortality, the specific impact on intracerebral haemorrhage (ICH) risk remains unclear. The relationship between sleep duration and the risk of ICH was investigated in our study.

Association between metabolic syndrome and functional outcome in patients with acute ischaemic stroke

There is a paucity of information on the role of metabolic syndrome (MetS) as a prognosticator after ischaemic stroke. We investigated the association between MetS and functional outcome in patients with acute ischaemic stroke.

Carotid cavernous fistula with cervical myelopathy

We report a patient with carotid cavernous fistula (CCF) presenting with cervical myelopathy. The patient initially presented with ocular pain accompanied by binocular diplopia and was diagnosed with Tolosa-Hunt syndrome at another institution. This patient experienced long-standing venous hypertension due to the delay in diagnosis. Posterior venous drainage from the CCF caused venous congestion in the brainstem and cervical spinal cord causing cervical myelopathy. Glue embolization using n-butyl-2-cyanoacrylate was attempted, but only partial embolization was possible because access to feeding arteries was limited. Stereotactic gamma-knife radiosurgery was performed as an alternative treatment, and effectively obliterated the CCF. However, the patient remained disabled due to cervical cord atrophy associated with long-standing venous hypertension.

Tachycardia burden in stroke unit is associated with functional outcome after ischemic stroke

Background Stroke unit care is associated with decrease in mortality and improvement in neurological outcome in patients with acute stroke. Heart rate is a commonly monitored variable in the stroke unit. However, little is known about tachycardia burden in the stroke unit and its association with outcome. Aims To investigate the effects of tachycardia burden in the stroke unit on functional outcome in patients with acute ischemic stroke. Methods We collected data from 246 patients with acute ischemic stroke admitted to our stroke unit between July 2013 and June 2014. Tachycardia burden was defined as duration of heart rate over 95 per minute divided by the total monitoring time, using the heart rate data sampled every 1 min. We divided the study population into quartiles of tachycardia burden and analyzed their association with poor three-month functional outcome (modified Rankin Scale score of ≥3). Results Among included patients (age, 67.4 u2009±u2009 12.8; male, 53.7%), tachycardia burden was 0.7% (median, interquartile range [0.1–5.7%]). The patients with higher tachycardia burdens were older, more likely to have higher stroke severity, cardioembolic etiology, atrial fibrillation, fever, pneumonia, higher initial glucose level, and higher white blood cell count. As compared with the lowest quartile (<0.1%), the highest quartile of tachycardia burden (≥6.0%) was significantly associated with poor outcome (adjusted odds ratio, 5.10; 95% confidence interval, 1.38–18.90; pu2009=u20090.01) after adjustment for covariates. Conclusions Patients with increased tachycardia burden during stroke unit stay have poor functional outcome. Countermeasures against worsening factors might be utilized for patients with increased tachycardia burden.

Cystatin C is a useful predictor of early neurological deterioration following ischaemic stroke in elderly patients with normal renal function

Introduction Cystatin C has been suggested as a sensitive marker of renal function. A high level of cystatin C is related to cardiovascular disease and stroke in elderly patients. We investigated the relationship between levels of cystatin C and early neurological deterioration with acute ischaemic stroke in elderly patients without chronic kidney disease. Patients and methods We evaluated a total of 771 elderly patients (mean age, 72.2; male, 59.0%) without chronic kidney disease who were admitted following acute ischaemic stroke between March 2010 and January 2015. The patients were divided into four groups based on the quartiles of serum cystatin C values. Early neurological deterioration was defined as an increase of ≥2 points from the baseline National Institutes of Health Stroke Scale score during the 7 days following onset. We compared the clinical characteristics and cystatin C concentrations between patients with and without early neurological deterioration. Results Eighty-six patients (11.2%) experienced early neurological deterioration. The percentage values of the higher (third and fourth) quartiles were significantly higher in the early neurological deterioration group (30.2% vs. 24.4% and 34.9% vs. 23.8%, Pu2009=u20090.002). After adjustment for covariates, higher cystatin C levels were independently associated with a higher risk of early neurological deterioration: odds ratio (95% confidence interval) for second quartile 1.59 (0.70–3.58), third quartile 2.75 (1.25–6.04), fourth quartile 3.12 (1.36–7.16); P for trend 0.026. Discussion and conclusions This study demonstrated that cystatin C concentrations in elderly patients without chronic kidney disease were associated with early neurological deterioration following acute stroke. This suggests that cystatin C level could be a useful predictor for early neurological deterioration following acute stroke.

Pretreatment with low-dose fimasartan ameliorates NLRP3 inflammasome-mediated neuroinflammation and brain injury after intracerebral hemorrhage

ABSTRACT Nucleotide‐binding and oligomerization domain‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome, which is composed of an NLRP3 domain, the adaptor molecule apoptosis‐associated speck‐like protein containing a CARD (ASC) domain, and procaspase‐1, plays an important role in the immune pathophysiology of the secondary damage induced by intracerebral hemorrhage (ICH). This study aims to investigate whether pre‐stroke treatment with fimasartan, an angiotensin II receptor blocker, has anti‐inflammatory effects on ICH by inhibiting the activation of the NLRP3 inflammasome. Sprague‐Dawley rats were divided into five groups: sham, vehicle, low‐dose (0.5mg/kg) and regular‐doses (1.0 and 3.0mg/kg) fimasartan. These rats were treated for 30days before the induction of collagenase‐induced ICH and continuously 3days after surgery. The mean blood pressure (BP) in the low‐dose fimasartan group was not significantly different from that of control, and BP in the regular‐dose groups was decreased in a dose‐dependent manner. Pretreatment with low‐dose fimasartan attenuated ICH‐induced edema and improved neurological functions. Activation of the NLRP3/ASC/caspase‐1 and the NF‐&kgr;B pathways after ICH was markedly reduced by low‐dose fimasartan. The double immunofluorescence staining of brain cells showed a significant decrease in the co‐localization of NLRP3 with Iba1 (microglia marker) positive cells by fimasartan treatment. Cultured microglia cells stimulated by hemolysate demonstrated significant activation of the inflammasome, which was reduced by fimasartan. Pretreatment with a low‐dose fimasartan alleviated brain damage after acute ICH by inhibiting the NLRP3 inflammasome without lowering MBP. Our study suggests pre‐stroke administration of fimasartan could potentially attenuate ICH‐induced secondary brain injury by targeting the inflammasome. HIGHLIGHTSNLRP3 inflammasome activation is involved in the secondary brain damage after ICH.Pre‐stroke treatment with low‐dose fimasartan has favorable effects on acute ICH injury.Fimasartan could potentially target the NLRP3 inflammasome to protect ICH injury independent of its effect on BP.