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ABSTRACT: INTRODUCTION: There is no single blood marker for prediction of prognosis in ischemic stroke. The combination of multiple blood markers may enhance the predictability of long-term outcome following ischemic stroke. METHODS: Blood concentrations of neuronal markers (NSE, VSNL-1, hFABP, and Ngb), astroglial markers (S100B and GFAP), inflammatory markers (IL-6, TNF-alpha, and CRP), blood-brain barrier marker (MMP-9), and haemostatic markers (D-dimer and PAI-1) were measured within 24 hours after stroke onset. The discrimination and reclassification for favorable and poor outcome were compared after adding individual or a combination of blood markers to the clinical model of stroke outcome. RESULTS: In multivariate analysis, natural log-transformed (log) IL-6 (odds ratio [OR]: 1.75, 95% CI: 1.25 - 2.25, P=0.001) and loghFABP (OR: 3.23, 95% confidence interval [CI]: 1.44 - 7.27, P = 0.005) were independently associated with poor outcome. The addition of a single blood marker to the clinical model did not improve the discriminating ability of the clinical model of stroke outcome. However, the addition of the combination of logIL-6 and loghFABP to the clinical model showed improved discrimination (area under receiver operating characteristic [AUROC] curve: 0.939 vs. 0.910, P = 0.03) and reclassification performance (net reclassification improvement [NRI] index: 0.18, P = 0.005). CONCLUSIONS: A combination of circulating IL-6 and hFABP level has an additive clinical value for prediction of stroke outcome.
Critical care (London, England) 03/2013; 17(2):R45. · 4.61 Impact Factor
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ABSTRACT: A healthy, 66-year-old, right-handed man was admitted to our university hospital and diagnosed with herpes zoster ophthalmicus (HZO). After 4weeks, he complained of hemichorea on his left side. Brain MRI showed a focal hemorrhage in the right subthalamic area. No evidence of aneurysmal lesion or cerebral angiitis was observed on cerebral angiography.
Journal of Clinical Neuroscience 02/2013; · 1.25 Impact Factor
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ABSTRACT: OBJECTIVES: No ideal blood marker exists for the diagnosis of ischemic stroke. Combined use of multiple blood markers would enhance the ability of clinical diagnosis of ischemic stroke. Design and methods Blood concentrations of neuronal markers (NSE, VSNL-1, hFABP, and Ngb), astroglial markers (S100B and GFAP), inflammatory markers (IL-6 and TNF-α), blood-brain barrier marker (MMP-9), and haemostatic markers (PAI-1) were measured within 6-24hours of stroke onset. The area under the receiver operator characteristic (AUROC) curve of patients with ischemic stroke and stroke-mimic was compared after adding individual or a combination of blood markers to the clinical diagnostic assessment (age, atrial fibrillation, and Face-Arm-Speech Test [FAST]). RESULTS: Despite acute elevations of blood IL-6, S100B, MMp-9, hFABP, and PAI-1 in univariate analysis, only IL-6, S100B, and MMP-9 were independently associated with ischemic stroke in multivariate analysis. The addition of biomarkers (IL-6, S100B, and MMP-9) did not improve the diagnostic performance of baseline clinical models with added biomarkers versus baseline clinical models alone (AUROC, 0.865 vs. 0.837, p=0.069). CONCLUSIONS: IL-6, S100B, and MMP-9 markers are elevated in the peripheral blood during the acute phase of ischemic stroke. However, the clinical usefulness of these biomarkers is limited due to low discriminating ability when compared to clinical parameters alone in diagnosis of ischemic stroke.
Clinical biochemistry 02/2013; · 2.02 Impact Factor
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ABSTRACT: BACKGROUND: Our aim was to investigate the impact of plasma total homocysteine (tHcyt) levels on cervico-cerebral atherosclerosis and cerebral small vessel ischemia in non-stroke individuals. METHODS: Demographic, laboratory, brain magnetic resonance imaging and magnetic resonance angiographic data were retrospectively analyzed in 682 non-stroke individuals. The association between plasma tHcyt and radiological indices of cervico-cerebral atherosclerosis (any presence of cervico-cerebral [aCC] atherosclerosis, extracranial [EC] atherosclerosis and intracranial [IC] atherosclerosis) and cerebral small vessel ischemia (silent brain infarct [SBI] and cerebral white matter hyperintensity [cWMH]) was analyzed after adjusting for cardiovascular risk factors. RESULTS: There was no association between values for natural log-transformed tHcyt (log-Hcyt) and aCC atherosclerosis, EC atherosclerosis, or IC atherosclerosis. The log-Hcyt was independently associated with cWMH (OR: 3.07, 95% CI: 1.64-5.75) and SBI (OR: 2.91, 95% CI: 1.57-5.40) in multivariate analysis. Median plasma tHcyt level increased as the severity of cWMH increased. CONCLUSIONS: Our results suggest that hyperhomocysteinemia plays a major role in the development of cerebral small vessel ischemia, but not in the development of atherosclerosis of major cerebral arteries.
Thrombosis Research 12/2012; · 2.44 Impact Factor
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ABSTRACT: Although metabolic syndrome (MS) is recognized as a risk factor for ischemic stroke, little is known about genetic variants that confer susceptibility to ischemic stroke among individuals with or without MS. This study was completed to investigate whether the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism is associated with MS as a risk factor for ischemic stroke in the Korean population. The prevalence of MS was significantly higher in ischemic stroke patients than controls (adjusted odds ratio [AOR]=1.420; 95% confidence interval [CI]=1.017-1.982, P=0.040). MS prevalence was also significantly different between patients with subtypes of small-artery occlusion (AOR=1.707; 95% CI=1.081-2.695, P=0.022) and large-artery occlusion (AOR=1.661; 95% CI=1.089-2.534, P=0.019) versus controls. The frequencies of the MTHFR 677 TT genotype (AOR=3.001; 95% CI=1.487-6.057, P=0.002) and CT genotype (AOR=1.772; 95% CI=1.053-2.983, P=0.031) of the MS group, and for the CC genotype in those without MS were significantly different between the ischemic stroke patients and controls. The MTHFR 677C>T polymorphism was associated with a higher risk of MS among ischemic stroke patients in the Korean population.
Neuroscience Letters 11/2012; · 2.11 Impact Factor
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ABSTRACT: OBJECTIVE: MicroRNAs play a role in atherosclerosis-related diseases, such as cerebrovascular or cardiovascular disease. However, the effect of miR-146a, miR-149, miR-196a2, and miR-499 polymorphisms on stroke and silent brain infarction (SBI) susceptibility has not been reported. METHODS AND RESULTS: Using polymerase chain reaction-amplified DNA, microRNA polymorphisms were analyzed in 678 patients with ischemic stroke, 373 patients with SBI, and 553 control subjects. The miR-146aC>G polymorphism and miR-146aG/-149T/-196a2C/-499G allele combination was significantly associated with ischemic stroke prevalence. For SBI prevalence, there were no statistically significant genetic markers. However, some allele combinations were associated with increased SBI incidence (C-T-C-G and G-T-T-A of miR-146a/-149/-196a2/-499). In subgroup analyses, miR-146aC>G increased stroke risk in female, normotensive, and nondiabetic groups. There were significant combined effects between microRNA polymorphisms and homocysteine/folate levels on ischemic stroke and SBI prevalence. CONCLUSIONS: The miR-146aG allele and miR-146aG/-149T/-196a2C/-499G allele combination were associated with ischemic stroke pathogenesis. The combined effects between microRNA polymorphisms and homocysteine/folate levels may contribute to stroke and SBI prevalence.
Arteriosclerosis Thrombosis and Vascular Biology 11/2012; · 6.37 Impact Factor
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ABSTRACT: OBJECTIVES: Heart-type fatty acid binding protein (H-FABP) is enriched in neuronal cell body as well as myocardium, and is rapidly released from damaged neuron into circulation in cerebral ischemia. We performed a comparative analysis between plasma H-FABP and S100B levels in the acute phase of ischemic stroke. METHODS: The present study included 111 consecutive patients with acute ischemic stroke and 127 control subjects. Measurement of plasma H-FABP and S100B levels was conducted during acute phase (<24h) of stroke. Clinical severities were evaluated by the use of NIHSS scores at admission and mRS score at 3 months after symptom onset. RESULTS: Both the plasma H-FABP and S100B levels were significantly higher in stroke group than control group. In multiple logistic regression analysis, statistical significance of both markers remained significant after adjusting the vascular risk factors. In the receiver operator characteristic (ROC) curve analysis, neither H-FABP (area under curve [AUC]=0.71, P<0.001, sensitivity: 59.5%, specificity: 79.5%) nor S100B (AUC=0.70, P<0.001, sensitivity: 54.0%, specificity: 83.5%) showed a favorable degree of diagnostic value to discriminate stroke from stroke mimic. Plasma H-FABP (r=0.46, P<0.01) and S100B (r=0.45, P<0.01) were correlated with initial NIHSS score, and both marker were significantly higher in patients with poor clinical outcome. CONCLUSION: Although plasma H-FABP is elevated in the acute phase of ischemic stroke, the diagnostic accuracy of H-FABP as a sole marker is not sufficient to be applied in the clinical setting. Plasma H-FABP can be used as a potential marker for stroke prognosis.
Clinical neurology and neurosurgery 07/2012; · 1.30 Impact Factor
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ABSTRACT: Peripheral blood cells and inflammatory mediators have a detrimental effect on brain during cerebral ischemia. We investigated the immunologic changes on peripheral blood in the acute phase of ischemic stroke using RNA microarray.
mRNA microarray and real time-polymerase chain reaction (RT-PCR) for genes of interest in microarray data were analyzed in 12 stroke patients and 12 controls. Plasma matrix metalloproteinase-9 (MMP-9) concentrations were measured in 120 stroke patients and 82 controls.
In microarray analysis, a total of 11 genes of interest showed different expression in patients with ischemic stroke. The three most highly expressed genes were C19orf59 (chromosome 19 open reading frame 59), MMP9 and IL18RAP (interleukin-18 receptor accessory protein), whereas gene with the lowest expression was GNLY (granulysin). The expression patterns of three selected genes (MMP9, IL18RAP and GNLY) were validated by RT-PCR. The plasma concentration of MMP-9 was significantly elevated in the stroke patients, and showed a weakly positive correlation with infarct volume. Gene set enrichment analysis (GSEA) showed that gene sets related to immunity and defense, signal transduction, transport and cell adhesion were significant in acute ischemic stroke.
In the peripheral blood, numerous genes of inflammatory mediators, including MMP9, IL18RAP and GNLY, are altered in the acute phase of ischemic stroke. This stroke-specific gene expression profiling provides valuable information about the role of peripheral inflammation to the pathophysiological mechanism of ischemic stroke.
Journal of neuroimmunology 05/2012; 249(1-2):60-5. · 2.84 Impact Factor
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ABSTRACT: BACKGROUND: The alpha2-adrenergic receptor (α2-AR) mediates physiological responses to endogenous catecholamine, and genetic variants of α2-AR may predispose to clinical vascular diseases. We evaluated whether common genetic variants of each three subtype of alpha2-adrenergic receptor (ADRA2A, ADRA2B, and ADRA2C) were associated with ischemic stroke. METHODS: A total of 616 patients with ischemic stroke and 512 controls were genotyped for the ADRA2A 1780G>A, ADRA2B 301-303 I/D, and ADRA2C 322-325 I/D polymorphisms. Logistic regression analyses, adjusting for multiple comparisons, were used to determine the association between the minor allele of each of three ADRA2 genes and the risk of ischemic stroke and pathophysiological subtypes. RESULTS: The ADRA2B 301-303 D allele was more prevalent in the stroke group, compared to controls (DD vs. II, OR: 1.78, 95% CI: 1.18-2.69; recessive, OR: 1.55, 95% CI: 1.06-2.26). A subgroup analysis revealed that this association was found only in the small vessel diseases (SVD) type (DD vs. II, OR: 1.92, 95% CI: 1.11-3.33). The ADRA2A and ADRA2C polymorphisms did not contribute to an increased risk of ischemic stroke or any pathophysiological subtype. CONCLUSIONS: The ADRA2B 301-303 D allele confers an increased risk of overall ischemic stroke and SVD subtype.
Clinical neurology and neurosurgery 05/2012; · 1.30 Impact Factor
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Young Seok Park,
Young Joo Jeon,
Hyun Seok Kim,
Kyu Young Chae, Seung-Hun Oh,
In Bo Han,
Hyun Sook Kim,
Won-Chan Kim,
Ok-Joon Kim,
Tae Gon Kim,
Joong-Uhn Choi,
Dong-Seok Kim,
Nam Keun Kim
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ABSTRACT: We conducted a case-control study to investigate whether vascular endothelial growth factor (VEGF -2578, -1154, -634, and 936) and kinase insert domain containing receptor (KDR -604, 1192, and 1719) polymorphisms are associated with moyamoya disease. Korean patients with moyamoya disease (n = 107, mean age, 20.9±15.9 years; 66.4% female) and 243 healthy control subjects (mean age, 23.0±16.1 years; 56.8% female) were included. The subjects were divided into pediatric and adult groups. Among the 64 surgical patients, we evaluated collateral vessel formation after 2 years and divided patients into good (collateral grade A) or poor (collateral grade B and C) groups. The frequencies and distributions of four VEGF (-2578, -1154, -634, and 936) and KDR (-604, 1192, and 1719) polymorphisms were assessed from patients with moyamoya disease and compared to the control group. No differences were observed in VEGF -2578, -1154, -634, and 936 or KDR -604, 1192, and 1719 polymorphisms between the control group and moyamoya disease group. However, we found the -634CC genotype occurred less frequently in the pediatric moyamoya group (p = 0.040) whereas the KDR -604C/1192A/1719T haplotype increased the risk of pediatric moyamoya (p = 0.024). Patients with the CC genotype of VEGF -634 had better collateral vessel formation after surgery. Our results suggest that the VEGF -634G allele is associated with pediatric moyamoya disease and poor collateral vessel formation.
PLoS ONE 01/2012; 7(10):e47158. · 4.09 Impact Factor
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ABSTRACT: Vascular endothelial growth factor (VEGF) plays a role in atherosclerosis-related diseases such as cerebrovascular or cardiovascular diseases. However, the effect of VEGF -2578C>A, -1154G>A, -634G>C, and 936C>T polymorphisms on the susceptibility to stroke and silent brain infarction has not been reported.
Using polymerase chain reaction-amplified DNA, VEGF polymorphisms were analyzed in 615 patients with ischemic stroke, 376 patients with silent brain infarction, and 494 control subjects.
The AA and CC+CA (C allele bearing) genotype frequencies of the -2578C>A polymorphism and the CT+TT (T allele-bearing) genotype frequency of the 936C>T polymorphism were significantly different between the stroke and control groups (false discovery rate-adjusted probability values of 0.016, 0.044, and 0.044, respectively). When stratified by the size of the occluded vessel, the VEGF polymorphisms were associated with patients with multiple small-artery occlusions. Several haplotypes of the VEGF polymorphisms were significantly different between the control and stroke groups. With respect to silent brain infarction, the difference in the frequency of the -634G>C polymorphism between the GC+CC (C allele-bearing) genotype and the controls was marginally significant (false discovery rate-adjusted probability value of 0.056). On the other hand, the -634G>C and 936C>T polymorphisms were associated with plasma homocysteine levels of patients with multiple or single small-artery occlusions, respectively.
This study suggests that VEGF polymorphisms and haplotypes are possible genetic determinants for the risk of ischemic stroke, particularly in patients with multiple small-artery occlusions. However, VEGF polymorphisms had only a weak association with plasma homocysteine levels in the Korean population.
Stroke 07/2011; 42(9):2393-402. · 5.73 Impact Factor
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ABSTRACT: Kinase insert domain-containing receptor (KDR), a type 2 vascular endothelial growth factor receptor, plays a crucial role in angiogenesis and vascular integrity of blood vessels. We evaluated whether single nucleotide polymorphisms (SNPs) and haplotype of kinase insert domain-containing receptor (KDR) are associated with increased risk of ischemic stroke in the Korean population.
Totals of 501 patients with ischemic stroke and 478 controls were screened for the KDR -604T>C, +1192G>A, and +1719A>T SNPs. Subgroup analysis was performed to determine whether the effect of KDR polymorphism is specific to certain etiological subtypes of ischemic stroke. In addition, haplotype frequencies of these three SNPs were analyzed in stroke patients and controls.
The SNP +1719T allele was associated with risk of ischemic stroke in a dose-dependent manner (TT vs. AA: adjusted OR: 1.90, 95% CIs: 1.29-2.81, p=0.001 and false discovery rate (FDR)=0.003). Subgroup analysis showed that the SNP +1719T allele had a slight but significant association with small vessel disease type (TT vs. AA: adjusted OR: 1.91, 95% CIs: 1.11-3.29, p=0.02). There was no association between SNP -604 and SNP +1192 and ischemic stroke risk. In haplotype analysis, the T-G-T (-604/+1192/+1719), T-A-T, and C-G-T haplotypes increased the relative risk of ischemic stroke.
The KDR +1719A>T polymorphism and its haplotypes are possible genetic determinants for the risk of ischemic stroke.
Journal of the neurological sciences 06/2011; 308(1-2):62-6. · 2.32 Impact Factor
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ABSTRACT: It is generally assumed that silent brain infarction (SBI) and symptomatic lacunar infarction (sLAC) share common vascular risk factors and their pathogeneses are known to be similar. However, few studies have conducted a risk factor profile analysis of the two diseases in a single study design.
This study included 64 subjects with SBI lesions, 140 patients with sLAC, and 342 controls by retrospective investigation of brain MRI. Topographic findings and vascular risk factor profiles were compared.
Compared to the controls, the SBI group was found to be associated with hypertension (p = 0.002) and elevated plasma total homocysteine level (p = 0.02). The sLAC group was found to be associated with hypertension (p = 0.001), diabetes (p = 0.004), smoking (p = 0.002), ischemic heart disease (p = 0.01) and hyperlipidemia (p = 0.04). In the present study, risk factor profiles of the SBI and sLAC were not exactly the same, indicating a different pathogenesis between the two diseases.
European Neurology 04/2011; 65(5):250-6. · 1.81 Impact Factor
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ABSTRACT: To evaluate the prevalence and to identify the risk factors of silent brain infarction (SBI) in patients with ischemic stroke.
A total of 395 consecutive patients with first-ever ischemic stroke that underwent brain MRI were enrolled in this study. The prevalences of vascular risk factors in a SBI-positive (n=132) and in a SBI-negative group (n=263) were compared. The prevalences and characteristics of SBI were further evaluated with respect to stroke subtype and periventricular white-matter hyperintensity (PWMH) lesion.
The frequency of SBI among the 395 study subjects was 33.4%, and 10.1% of the study subjects had multiple-SBI lesions. The most common lesion site was basal ganglia (47%). Multiple logistic regression analysis showed that hypertension (OR: 1.94, 95% CI: 1.22-3.07, P=0.005) and the presence of an advanced PWMH lesion (OR: 1.77, 95% CI: 1.06-2.96, P=0.030) were significantly associated with SBI. Furthermore, an advanced PWMH lesion (OR: 2.88, 95% CI: 1.19-6.95, P=0.010) was more associated with multiple-SBI lesions than with a single-SBI lesion. The frequency of SBI was higher among those with the small-vessel disease type (45.5%) than in those with the large-artery disease (32.5%) or cardioembolic stroke type (25.6%) (P=0.04).
The prevalence of SBI in patients with ischemic stroke was found to be high, and hypertension was found to be the most important risk factor of SBI. Small-vessel disease and a diffuse white-matter lesion were found to be closely associated with SBI, and especially with multiple-SBI lesions.
Journal of the neurological sciences 03/2010; 293(1-2):97-101. · 2.32 Impact Factor
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ABSTRACT: The aims of this study were to evaluate the role of tumor necrosis factor-α (TNF-α) polymorphisms in patients susceptible to ischemic stroke and silent brain infarction (SBI), and to determine the relationship between TNF-α polymorphisms and plasma total homocysteine (tHcy) levels.
We studied 237 patients with ischemic stroke, 257 patients with SBIs, and 216 control subjects. For control subjects, we selected healthy individuals matched for gender and age from those individuals who came to our hospital for health examinations. The TNF-α-308G→A and -238G→A genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism method.
The frequency of the TNF-α-308G→A polymorphism was significantly different between the patients with ischemic stroke and the control group (GG vs. GA+AA; adjusted odds ratio, AOR, 0.50; 95% CI 0.255-0.989). By subgroup analysis, when tHcy levels were stratified into high (>10.80 μmol/l), moderate (8.21-10.80 μmol/l), and low levels (<8.21 μmol/l), the frequency of the TNF-α-308GA+AA genotype in the highest tertile group was higher than in the lowest tertile group (AOR 2.46; 95% CI 1.063-5.699). However, the relationship between SBI susceptibility and polymorphisms of TNF-α was not established. The tHcy levels were significantly and inversely correlated with folate levels in the TNF-α-308GG and TNF-α-238GG genotypes in the ischemic stroke, SBI, and control groups (p< 0.05).
Our results suggest that the TNF-α-308G→A polymorphism is responsible for susceptibility to ischemic stroke and is associated with high tHcy levels in Koreans.
Cerebrovascular Diseases 01/2010; 30(5):483-90. · 2.72 Impact Factor
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ABSTRACT: Although prompt diagnosis and emergent surgical intervention are important in acute spinal subdural hematoma (SSDH), some cases with spontaneous remission of symptom and hematoma without surgery have been reported. We present a case of acute nontraumatic SSDH presenting with transient left hemiplegia for 4 hours. A magnetic resonance imaging study of cervical spine confirmed SSDH with C3-6 cervical cord compression at the left side. The patient had conservative management without recurrence. Although hemiplegia is an unusual clinical manifestation of SSDH, it should be differentiated from that of cerebrovascular origin promptly. Conservative management may be an alternative therapeutic option for selective cases with transient neurological deficits.
Journal of Korean Neurosurgical Society 07/2009; 45(6):390-3. · 0.60 Impact Factor
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ABSTRACT: Cerebral embolic infarction is the most common neurologic complication of cardiac myxoma (CM). Development of cerebral aneurysms in CM is very rare. We present a 64-year-old woman with acute cerebral infarction and multiple cerebral aneurysms complicated by CM. The aneurysms were multiple, fusiform-shaped, and located in distal branch of major cerebral arteries. The serum interleukin (IL)-6 was highly elevated, which was normalized after surgical resection of CM. There was no regression of aneurysms on follow-up neuroimaging. Multiple cerebral aneurysms in CM are rare condition. Highly elevated serum IL-6 may be associated with increased risk of cerebral aneurysmal formation.
Journal of Korean Neurosurgical Society 07/2009; 45(6):394-6. · 0.60 Impact Factor
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Journal of Clinical Neuroscience 07/2009; 16(9):1252-3. · 1.25 Impact Factor
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ABSTRACT: Transient global amnesia (TGA) patients were retrospectively reviewed to determine the usefulness of high-field strength MRI in detecting probable ischemic lesions in TGA.
We investigated the lesion detection rate in patients with TGA using 1.5T and 3.0T MRI. Acute probable ischemic lesions were defined as regions of high-signal intensity in diffusion weighted image with corresponding low-signal intensity in apparent diffusion coefficient map.
3.0T MRI showed 11 out of 32 patients with probable ischemic lesions in the hippocampus with mean lesion size of 2.8 +/- 0.6 mm, whereas 1.5T MRI detected no lesion in any of 11 patients. There were no significant differences in clinical characteristics between the groups of 1.5 and 3.0T MRI.
High-field strength MRI has a higher detection rate of probable ischemic lesions than low-field strength MRI in patients with TGA.
Yonsei medical journal 05/2009; 50(2):211-4. · 0.77 Impact Factor
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Movement Disorders 01/2009; 24(3):463-4. · 4.51 Impact Factor
