Search

Introduction: Although the association between vertebral artery or posterior inferior cerebellar artery dissection and lateral medullary infarction (LMI) has been established, the actual prevalence of dissection among patients with LMI may still be underestimated. Methods: Consecutive patients with acute pure LMI admitted between 2010 and 2021 were included. High-resolution vessel wall MRI (VWMRI) and/or transfemoral cerebral angiography (TFCA) were performed in a part of patients and were regarded as gold standard tests for diagnosis of dissection. Factors associated with definite dissection based on VWMRI or TFCA findings were assessed. Risk scoring for dissection was created based on multivariate logistic regression and applied to estimate the number of possible dissection. Results: Eighty-seven LMI patients were eligible and 47 (54.0%) of them underwent VWMRI (n=43) and/or TFCA (n=7). Among these 47 cases, 24 were definite dissection. Three out of 40 patients without gold standard tests were diagnosed with definite dissection based on conventional MRI findings. Preceding headache and normal body weight were independently associated with dissection in LMI patients. A risk scoring which includes age, body mass index, and headache predicted dissection with 91.7% sensitivity and 69.6% specificity (area under the receiver operating characteristic curve, 0.889; 95% confidence intervals, 0.802-0.977) in our population. Additional nine out of 37 patients without gold standard tests nor diagnosis of definite dissection in conventional MRI could be considered as possible dissection based on the scoring. Definite and possible dissections together comprised 41.4% (n=36) of LMI in our study. Conclusions: Arterial dissection may be more prevalent among LMI patients than reported before. Thorough diagnostic effort for dissection is necessary based on scrutinizing risk stratification.

Introduction: White matter hyperintensities (WMH) are reportedly increased in moyamoya disease (MMD); however, their clinical importance is not well-established owing to their pathophysiological heterogeneity by distribution. This study aimed to evaluate the burden and pattern of WMH and its clinical implications in the MMD trajectory. Methods: Adult MMD patients without significant structural lesions were 1:1 propensity score-matched with healthy controls for sex and vascular risk factors. The total, periventricular, and subcortical WMH volumes were segmented and quantified fully automatically. WMH volumes were detrended by age and compared between the two groups. MMD severity based on Suzuki stage and future ischemic events were assessed for their association with WMH volumes. Results: A total of 190 pairs of patients with MMD and controls were analyzed. MMD significantly correlated with increased total (B, 0.086; standard error [SE], 0.027; p=0.002) and periventricular WMH volumes (B, 0.079; SE, 0.025; p=0.002). In the MMD subgroup, advanced MMD had an independent positive association with the total (B, 0.124; SE, 0.034; p Conclusions: Periventricular WMH, but not subcortical WMH, may represent the main pathophysiology of MMD. Periventricular WMH may be used as a marker for ischemic vulnerability in patients with MMD.

Introduction: Alteration of the gastrointestinal (GI) tract by resection or bypass surgery might affect the absorption of both warfarin and direct oral anticoagulants (DOACs). The clinical trials of DOACs excluded individuals with altered GI tract, hence there are limited pharmacokinetic data for them. Only several cases have been reported suggesting atrial fibrillation-related stroke due to reduced absorption of DOACs after GI surgery. We aimed to investigate the efficacy of warfarin and DOACs who underwent GI surgery using nationwide population-based data. Methods: This was a retrospective cohort study using claim-based national data from 2013 to 2020 from Korean Health Insurance Review and Assessment Service (HIRA). Patients with nonvalvular AF (NVAF) taking oral anticoagulants (OACs) were included. The patients taking OACs due to other indications than NVAF were excluded. Cox proportional hazard models with time-varying covariates were used to investigate the impact of GI surgery in patients taking warfarin and DOACs. Results: Of the 311,782 patients (mean age 72, male 56.7%) with NVAF, 3,807 underwent GI surgery. Warfarin and DOACs were prescribed in 14.3% and 85.7% of the patients, respectively. Overall, warfarin was associated with a higher risk of ischemic stroke compared with DOACs (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.44-1.59). In the GI surgery group, the hazard ratio for ischemic stroke for warfarin compared with DOACs was 2.70 (95% CI, 1.63-4.45, Figure). In the no GI surgery group, warfarin also had a higher risk of ischemic stroke compared with DOACs (HR 1.51, 95% CI 1.44-1.59). Among DOAC-treated patients, GI surgery was not associated with a risk of ischemic stroke (HR 0.87, 95% CI 0.67-1.12). Conclusions: DOACs were more effective for stroke prevention than warfarin in patients with NVAF whose GI tracts were altered due to previous surgery. GI surgery did not affect the risk of stroke in patients with NVAF taking DOAC.

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) has been linked with incident cardiovascular disease and its outcome. However, the association between CHIP and acute ischemic stroke is not yet fully elucidated. Methods: This retrospective, observational cohort study included 366 acute ischemic stroke patients from a single center prospective stroke registry and 4,628 general population control (age over 40 years old). We compared the prevalence of CHIP between stroke patients and control groups. A multivariable linear or logistic regression model was used to assess the association between CHIP and initial stroke severity, hemorrhagic transformation and functional disability at 90-day (modified Rankin scale score >1) after stroke. The contribution of individual CHIP driving genes was also evaluated. Results: When comparing the acute ischemic stroke patients (N=366) and the general population (N=4,628), the prevalence of CHIP was significantly higher in stroke patients than in the general population (32.0% vs. 13.9% with variant allele frequencies of 1.5%, p Conclusion: CHIP was obviously increased in ischemic stroke patients. Furthermore, CHIP was significantly associated with stroke severity, hemorrhagic transformation, and functional disability at 90 days.

Background and Purpose: Data on the effect on vascular outcomes of concomitant atherosclerotic vascular disease (ASVD) with atrial fibrillation (AF) after stroke are limited. This study evaluated the effect of ASVD with AF versus AF only on the risk of vascular events. Methods: We retrospectively analyzed a prospectively registered multicenter database involving 3213 stroke patients with AF. ASVD included extracranial atherosclerosis measured in the proximal portion of the internal carotid artery, intracranial atherosclerosis (all ≥50% stenosis), coronary artery disease, and peripheral artery disease and was categorized into 4 strata depending on the number of ASVDs (0, 1, 2, and 3–4). The independent associations of ASVD with major adverse cardiovascular events, stroke, and all-cause death were assessed. Results: A total of 2670 patients were included (mean age, 73.5±9.8 years; median CHA 2 DS 2 -VASc score, 5; interquartile range, 4−6). During the follow-up (mean, 1.7 years), a total of 672 (25.2%) major adverse cardiovascular events, 170 (6.4%) stroke events, and 501 (18.8%) all-cause deaths were noted. The adjusted hazard ratio for major adverse cardiovascular events versus no ASVD was 1.25 (95% CI, 1.00–1.56) for ASVD 1, 1.34 (95% CI, 1.02–1.76) for ASVD 2, and 1.93 (95% CI, 1.24–2.99) for ASVD 3–4. The adjusted hazard ratio for all-cause death versus no ASVD was 1.32 (1.01–1.74), 1.47 (1.06–2.03), and 2.39 (1.47–3.89), respectively. Among ASVD components, the presence of symptomatic or asymptomatic extracranial atherosclerosis was a more potent predictor of major adverse cardiovascular events (1.27 [1.05–1.54]) and all-cause death (1.45 [1.17–1.81]). Conclusions: ASVD burden with AF can be a cumulative marker of a high risk for untoward vascular outcomes. Among ASVD components, extracranial atherosclerosis seems to have a predominant effect.

Background: Recent clinical evidence supports the early initiation of aspirin and clopidogrel combination for patients with minor stroke or high-risk transient ischemic attack (TIA) to prevent stroke recurrence. However, some of the patients still experience early neurological deterioration (END) despite optimal antithrombotic treatment. We investigated clinical and laboratory variables related to END after optimal antithrombotic treatment among the patients with non-cardioembolic stroke or TIA. Methods: The patients with minor neurological deficit who received aspirin and clopidogrel within 24 hours after symptom onset were selected from the prospective stroke registries of Seoul National University and Chung-Ang University Hospital, in Seoul, Korea. The END due to ischemic stroke (END_IS) was defined as two or more national institute health stroke scale increase within 5 days after stroke which us due to stroke progression or recurrence. Included patients were divided into two groups according to the presence of END_IS and demographic and laboratory variables were compared between the two groups. Multivariable logistic regression analysis was performed to assess the independent predictors of the END. Results: During the study period from January 2015 to January 2021, 33 (8.7%) out of 380 patients experienced END_IS. In multivariate analysis, independent predictors of END_IS were the presence of intracranial artery stenosis ≥ 50% (odds ratio [OR] 2.922, [95% CI, 1.342-6.364], p=0.007), higher initial NIHSS score, (OR 1.502 [95% CI 1.120-2.015], p=0.007), previous use of statin (OR 0.282 [95% CI 0.080-0.990], p=0.007) and higher serum D-dimer level (OR 1.408 [95% CI, 1.074-1.847], p=0.048). Conclusions: Intracranial artery stenosis, stroke severity, previous statin use, and D-dimer level were the independent predictors of END_IS after dual-antiplatelet treatment in patients with minor stroke. Future studies are necessary to develop an additional therapeutic strategy for the at-risk patient group.

Background: Intracranial internal carotid artery calcifications (IICAC), considered a phenomenon within the spectrum of atherosclerosis and vascular aging, are frequently encountered in ischemic stroke patients. While intimal IICAC directly contributes to ischemic stroke pathophysiology, the medial counterpart is generally deemed as a risk factor for vascular end-points. Apart from aging and cardiovascular risk factors, the underlying pathophysiology that contributes to development of IICAC is not well understood; herein we studied the interplay between mineral and skeletal metabolism biomarkers, and IICAC presence and pattern. Methods: In a prospective series of 194 ischemic stroke patients (mean±SD age: 69±14 yr), blood samples were collected to determine calcium, phosphorus, magnesium, osteocalcin, parathyroid hormone, and vitamin D levels within 72 hours of symptom onset. IICAC presence and type was determined on admission CT-angiography source images; a medial or intimal type of IICAC category was assigned according to Kockelkoren criteria. Results: A total of 45 (23%) patients had no calcifications, while 95 (49%) had an intimal pattern and 54 (28%) had non-intimal (or medial) pattern. Apart from the well-known factors related with IICAC, such as age, lower glomerular filtration rate (GFR), history of hypertension, diabetes mellitus, coronary artery disease and atrial fibrillation, we identified admission magnesium levels to be associated with IICAC presence and pattern (no calcification: 1.96±0.18 mEq/L, intimal calcification 1.93±0.19 mEq/L, medial calcification: 1.81±0.28 mEq/L; p=0.006). None of the other biomarkers had any significant relationship to IICAC. In multivariate models, a lower magnesium level was significantly associated with medial calcification (each 0.1 mEq/L drop increased the odds by 1.2 (95% CI 1.0-1.4; p=0.046)), in addition to older age, history of diabetes mellitus and lower GFR. Conclusion: Hypomagnesemia is one of the factors well-known to be associated with vascular calcifications in the body. Our findings, extend this relationship to the intracranial vascular bed. No similar association was observed for other biomarkers related to mineral and skeletal metabolism. (Funding: TUBITAK grant 218S753)

Background: The thrombus retrieved from mechanical thrombectomy among stroke patients could provide important information regarding stroke mechanism and its prognosis. We investigated microRNA expression pattern from thrombus to differentiate stroke mechanism. Methods: Between September 2016 and March 2019, acute ischemic stroke patients who received intra-arterial mechanical thrombectomy from Chung-Ang University Hospital, Seoul, Korea were eligible to be included. After obtaining informed consent, the thrombus was stored at -70°C nitrogen tank. First, we performed microRNA microarray analysis for the patients with clearly identified stroke mechanisms including large artery atherosclerosis, cardioembolism with atrial fibrillation and cardioembolism with valvular heart disease. Second, those microRNAs derive from microarray analysis were validated by quantitative real time polymerase chain reaction, and correlation analyses were performed between microRNA levels and clinical data. Finally, the expression levels of microRNAs were compared between the patients with early neurological deterioration (END) after stroke and those without. Results: A total of 48 thrombi had been retrieved from 51 patients. The microarray analysis of microRNA revealed that 42 microRNAs were significantly altered among the three groups out of 869 examined microRNAs. Ejection fractions were negatively correlated with miR-450b-5p levels (r=-0.448, p Conclusion: The microRNA expression pattern can provide information regarding stroke mechanisms, underlying heart dysfunction and prognosis after recanalization treatment.

Background: Lipoprotein(a) is known to be associated with increased atherosclerotic burden and vascular event. We investigated the relationship between lipoprotein(a) level and cerebral arteriosclerosis burden, including both atherosclerosis and small vessel disease. Methods: Consecutive patients with acute cerebral infarction or transient ischemic attack who had been through both brain imaging and serum lipoprotein a level analysis were included in the study. For cerebral atherosclerosis, intracranial arterial calcification status at cavernous portion of internal carotid artery and cerebral atherosclerosis score as the sum of major cerebral arterial stenosis were measured from brain CT angiography. Assessed cerebral small vessel disease phenotype included white matter hyperintensities, old lacune, cerebral microbleeds and extensive perivascular space. The patients were categorized into four groups according to the predefined cut-off values of lipoprotein(a) (15, 30, 50mg/dL). Results: A total of 990 patients were included with 457 female patients (mean age = 68.2 ± 12.8 years). Overall cerebral atherosclerosis score or total small vessel disease burden was not increased according to increased lipoprotein(a) group, although the proportion of the patients with severe calcification showed increasing tendency. Multivariable logistic regression analysis revealed that increased lipoprotein(a) was independently associated with severe calcification (group 4, odds ratio = 1.68, confidence interval = 1.01 – 2.80). Increased lipoprotein(a) was associated with the presence of white matter hyperintensities and extensive perivascular space, but not associated with old lacune or cerebral microbleed. Conclusion: Lipoprotein(a) is independently associated with severe calcification of intracranial artery. The impact of elevated lipoprotein(a) toward small vessel disease burden seems to be different according to its phenotype.

Background: Arterial stiffness has been reported to be associated with hypertension, vascular disease including cerebral small vessel disease and increased mortality. Also, dyslipidemia is one of the potent risk factors for atherosclerosis. We aim to investigate the association of arterial stiffness and various lipid fractions including low density lipoprotein cholesterol (LDL-cholesterol), lipoprotein(a), and apolipoprotein B 100 in patients with acute ischemic stroke. Methods: We identified 2187 consecutive patients with acute ischemic stroke confirmed on MR imaging or CT. Brachial-ankle pulse wave velocity (baPWV) was measured using a volume-plethysmography device (VP-1000; Collin, Komaki, Japan). Lipid fractions were measured with blood sample taken after at least 8-hour fast. Vascular risk factors and demographics of patients were assessed by our prospectively collected stroke database. The association between baPWV and lipid fractions was tested using linear regression analysis. Results: Mean age of patients was 68.5 +/- 12.3 years and male was 1214 (55.5%). Mean baPWV was 20.85 +/- 5.55 m/sec. On simple regression analysis, baPWV was associated with lipoprotein(a) and LDL-cholesterol (p < 0.05). However, on multivariable linear regression adjusting for age, sex, lipid fractions and other vascular risk factors, apolipoprotein B 100 was the only significant lipid fraction for baPWV (beta 1.42; 95% confidence interval 0.45 - 2.40; p < 0.001). We included LDL-cholesterol instead of apolipoprotein B 100 in another model due to multicollinearity, which showed that neither LDL-cholesterol nor lipoprotein(a) was significant. Conclusion: Among lipid fractions, apolipoprotein B 100 is associated with systemic arterial stiffness in patients with acute ischemic stroke. Our finding suggests that apolipoprotein B 100 might be a better predictor for arterial stiffness than LDL-cholesterol and lipoprotein(a).

Introduction: Serum uric acid has been reported to be associated with arterial stiffness and cardiovascular disease in previous studies. However, some of them showed contradicting results. Also, some studies reported gender difference in the association between uric acid and vascular disease. We investigated whether serum uric acid is associated with arterial stiffness, blood pressure, and stroke in both genders. Methods: A total of 54,164 subjects who underwent health check-ups including brachial-ankle pulse weave velocity (baPWV) between 2004 and 2015 were enrolled. The average of the baPWV values obtained on both sides was used for further analysis. Past medical history was investigated through interview. Multivariable linear and logistic regression were used for the evaluation of association between serum uric acid and vascular outcomes. Results: Mean age was 45 ± 12 and male was 45,941 (85%). History of hypertension was in 10,278 (19%) and stroke in 460 (0.9%). Systolic blood pressure was 118 ±13 and diastolic blood pressure was 75 ± 9. baPWV was 1387 ± 223 cm/s. On multivariable linear regression, serum uric acid was associated with baPWV (beta 14.1; 95% CI 9.45 - 18.8), systolic blood pressure (beta 0.82; 95% CI 0.50 - 1.15), diastolic blood pressure (beta 0.57; 95% CI 0.34 - 0.80), and pulse pressure (beta 0.25; 95% CI 0.04 - 0.47). When we performed the same analyses in population without hypertension and stroke, the results did not change. On multivariable logistic regression, serum uric acid was associated with hypertension (odds ratio 1.42; 95% CI 1.33 - 1.51) and stroke (odds ratio 1.30; 95% CI 1.03 - 1.63). Conclusion: We showed that serum uric acid is significantly associated with arterial stiffness, various measures of blood pressure, hypertension and stroke in this single large cohort, irrespective of gender.

Background: While transthoracic echocardiography (TTE) is performed to find out potential embolic sources and certain cardiac abnormalities as a routine workup of stroke, clinical implication of echocardiographic findings for long-term outcomes in atrial fibrillation (AF)-related stroke patients has been unknown. Methods: This was a sub-study of K-ATTENTION (Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts), a multicenter-based cohort composed of prospective stroke registries from 11 tertiary centers. All stroke survivals enrolled in this study underwent TTE during hospitalization. Echocardiographic findings included left atrial (LA) diameter, left ventricular ejection fraction (LVEF), LV end-diastolic dimension (LVEDV), stenosis and regurgitation of mitral and aortic valves, and peak trans-mitral filling velocity/mean mitral annular velocity during early diastole (E/e’ ratio). Indexed-LA size was acquired as dividing LA size by body surface area. LV systolic function was grouped into normal (LVEF≥55%), mild (55%>LVEF>40%), and severe (LVEF≤40%). Level of E/e’ ratio associated with LV filling pressure was divided into normal ( Results: A total of 1952 patients were finally included. Over a mean follow-up of 1.72±1.31 years, 140 patients had recurrent stroke, 36 had coronary artery disease, and of 236 fatalities, 33 died of a vascular cause. Multivariable analyses demonstrated that severe LV systolic dysfunction was associated with a higher risk of coronary artery disease (hazard ratio [HR] 3.80, 95% confidence interval [CI] 1.53-9.41), vascular death (HR 3.59, 95% CI 1.42-9.10) and all-cause death (HR 2.29, 95% CI 1.47-3.56). Conclusions: LV ejection fraction could be important predictor for long-term outcomes in AF-related stroke.

Background and Purpose: Little is known about the different effect of outcomes and factors associated with vascular outcomes in stroke patients with atrial fibrillation in real world practice setting especially in Korea. In this study, we investigated the effect of each oral anticoagulants on vascular outcomes using K-ATTENTION (Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts) study. Methods: Consecutive data of acute stroke patients with atrial fibrillation were collected from 11 centers in Korea from January 2013 to December 2015. Eligibility of inclusion was acute stroke within 7 days from the onset of stroke and diagnosis of non-valvular or valvular atrial fibrillation. Vascular outcomes included ischemic stroke, hemorrhagic stroke, death of any cause, and major adverse cerebro/cardiovascular events (MACE). To describe the effect of each oral anticoagulants on vascular outcomes, we performed time-dependent Cox’s regression analyses with the class of oral anticoagulant as a time dependent covariate. For stroke, hemorrhagic stroke, and any stroke, death was considered as competing risk. Results: Among 3213 stroke patients included in K-ATTENTION study, a total 3033 stroke patients (mean age 73.45 ± 9.93 years old, female 48.5%) were included. Mean CHA2DS2-VASc score was 4.89 ± 1.37. During the study period, a total of 161 ischemic strokes, 46 hemorrhagic strokes, 199 any strokes, 556 death and 720 MACE were captured. Time-dependent Cox’s regression analysis revealed that use of oral anticoagulants [vitamin K antagonist (VKA), dabigatran, rivaroxaban, or apixaban] was associated with significantly lower risk of death and MACE compared with no oral anticoagulants use. Although, there was no difference among oral anticoagulants for ischemic stroke, hemorrhagic stroke, or any stroke when compared with no oral anticoagulants, dabigatran showed a trend of reduced risk of any stroke (HR 0.48, 95%CI 0.23 - 1.01, p = 0.0545). Conclusion: This real-world data revealed that the use of oral anticoagulants was associated with the reduced risk of MACE and death. However, for ischemic stroke and hemorrhagic stroke, the results were not conclusive. Dabigatran showed a trend of reduced risk of any stroke.

Introduction: Elevated Blood pressure (BP) is known to be related to hemorrhagic transformation (HT) after ischemic stroke. However, the effect of BP variation on the HT remains unclear, especially in patients with successful recanalization after mechanical thrombectomy. Hypothesis: Therefore, we investigated the relationship between BP and HT after mechanical thrombectomy following ischemic stroke. Methods: A consecutive 141 patients with acute ischemic stroke and successful recanalization (TICI 2b or TICI 3) were included for the analysis between January 2013 and November 2016. The information on BP was obtained over the first 24 hours using various parameters including mean, maximum (max), minimum (min), difference between max and min (max– min), standard deviation (SD), coefficient of variation (CV), and successive variations (SV) for systolic, diastolic BP, and mean BP. We defined major HT as a parenchymal hematoma type 2 (PH2). Result: Among the included patients (age, 66.3; and male. 55.2%), 16 patients (11.3%) developed major HT over the first 24 hours after successful recanalization. Systolic BP max-min was significantly increased in patients with major HT compared to those without major HT (61.2 mmHg vs. 44.2 mmHg, P = 0.034) while other BP parameters were not. In addition, systolic BP max-min was significantly associated with symptomatic HT (n=11, 7.8%, P = 0.007). After adjusting for confounders, systolic BP max-min was independently associated with major HT (Odds ratio, 1.028; 95% confidence interval, 1.004-1.051). Conclusions: Our results demonstrated that absolute change of systemic BP over the first 24 hours was associated with major and symptmatic HT after successful mechanical thrombectomy after acute ischemic stroke. This suggests that maintaining stable systolic BP is an important factor in possibly preventing major HT after successful recanalization.

Background and Purpose— The aim of this study was to determine the association between 25-hydroxyvitamin D (25(OH)D) and neuroimaging correlates of cerebral small vessel disease. Methods— We identified 759 consecutive patients with acute ischemic stroke or transient ischemic attack. Lacunes, white matter hyperintensity, and cerebral microbleed (CMB) were assessed using MR images. Deep CMB was defined as the presence of CMB in basal ganglia, thalamus, or brain stem. The association between 25(OH)D and small vessel disease was tested using linear and logistic regression analyses. Results— Mean age was 68 (±13) years. Mean level of 25(OH)D was 34.1±17.8 nmol/L. On bivariate analysis, a 25-nmol/L decrease in 25(OH)D was associated with lacunes (regression coefficient, 0.23; 95% confidence interval [CI], 0.02–0.45), severe white matter hyperintensity (odds ratio, 2.05; 95% CI, 1.41–3.08), and deep CMB (odds ratio, 1.28; 95% CI, 1.01–1.63). Also, 25(OH)D deficiency (≤25 nmol/L) was associated with lacunes (regression coefficient, 0.5; 95% CI, 0.04–0.95), severe white matter hyperintensity (odds ratio, 2.74; 95% CI, 1.31–6.45), and deep CMB (odds ratio, 1.68; 95% CI, 1.03–2.78). The association remained significant even after multivariable adjustment and in the subgroup of previously healthy patients. Conclusions— 25(OH)D is inversely associated with lacunes, white matter hyperintensity, and deep CMB. Our findings suggest that 25(OH)D is linked to small vessel disease, and in future trials it should be tested whether 25(OH)D supplementation can prevent small vessel disease.

Background: Arterial stiffness aggravation is known to increase cerebral small vessel disease burden. We investigated the association between brachial-ankle pulse wave velocity (baPWV) and the topography of MRI visible perivascular space in acute stroke population. Method: We analyzed clinical and laboratory data of acute ischemic stroke or transient ischemic attack patients who had been admitted to Chung-Ang University Hospital within 7 days after symptom onset between January 1st 2014 and May 31th 2015. We included those patients who underwent both brain MR imaging including T2 weighted sequence and baPWV. The topography of perivascular space was examined in basal ganglia and centrum semiovale level with validating scale (score 0-4), and dichotomized as low (score3). Result: A total of 481 patients were included (mean age 68.2±12.3, 44.7% male). When the distribution of baPWV were divided into quartile, the proportions of high PVS in basal ganglia was 10%, 20%, 40% and 40%, respectively. The proportion of high PVS in centrum semiovale was 20%, 40%, 36%, and 49%, respectively. Multivariate logistic regression analysis revealed that the high degree of basal ganglia PVS was associated with baPWV>2255cm/s (odds ratio 1.7, confidence interval 1.0-2.7, p=0.048) after adjusting age>70 years, hypertension, current smoking status and previous stroke history. The high degree of centrum semiovale PVS showed marginal association with baPWV>2255cm/s (odds ratio=1.4, confidence interval 0.9-2.3, p=0.137) after adjusting age>70 years and hypertension. Conclusion: Our pilot study suggests potential pathophysiological association between arterial stiffness and PVS topography.

Introduction: Arterial calcification is known to be related with atherosclerosis burden and future vascular event. Obesity has been suggested as a risk factor of coronary artery calcification. In this study we investigated association between intracranial arterial calcification and body mass among stroke population. Subject and Method: Between January 2008 and December 2013 acute cerebral infarction patients who were hospitalized in Chung-Ang University Hospital were eligible to be included. The patients with brain computed tomographic angiography were included, and intracranial arterial calcification was examined from cavernous portion of internal carotid artery. Underweight, normal, overweight and obesity groups were divided according to body mass index (BMI). Univariable and multivariable analysis was conducted to examine association between body mass and intracranial arterial calcification. Results: A total of 1231 patients was included (mean age, 67.4 years old; percentage of male gender, 57.8%; mean BMI, 23.7kg/m2), with 4.9% of underweight, 37.6% normal weight, 26.3% overweight and 31.2% obese patients. Advanced arterial calcification, defined as calcification involving at least 1 cm length or more of both intracranial internal carotid arteries was found in 281 patients (22.8%). The association between obesity and advanced arterial calcification was not significant [odds ratio (OR) 0.76, 95% confidence interval (CI) 0.56-1.02, p=0.064]. However, the underweight group had significantly more advanced arterial calcification compared to normal group (OR 2.95, 95% CI 1.74 - 5.01, p Conclusion: This study presents the association of weight and calcification of intracranial vessels in stroke population, and underweight defined as BMI less than 18.5kg/ m2 is related to advanced arterial calcification. Future studies are warranted to evaluate pathophysiological mechanism of intracranial arterial calcification and lean body mass.

Background: The prediction of stroke progression after acute cerebral infarction is important for clinician to determine high risk patient group for close observation and proactive management. We sought to find imaging biomarker which predicts neurological deterioration after acute cerebral infarction. Methods: Between January 2008 and June 2013, those acute infarction patients who admitted Chung-Ang university hospital within seven days after symptom onset were eligible to be included. We selected the patients who had been through both brain CT angiography and brain MR imaging (MRI) including susceptibility weighted image and FLAIR. The presence of white matter hyperintensity, asymptomatic lacune, and cerebral microbleed were assessed from initial brain MRI, and intracranial vascular calcification was analyzed from both intracranial internal carotid arteries by brain CT angiography. Stroke progression was defined as two or more National Institutes of Health Stroke Scale progression during admission. Univariate analysis followed by multivariate logistic regression analysis was performed to find independent imaging parameter which predicts stroke progression. Results: A total of 724 patients were included in the study period. Univariate analysis showed that severe calcification involving both distal internal carotid artery more than 1 centimeter and/or 50% of vessel diameter (p=0.006), white matter hyperintensity with Fazekas grade 3 (p=0.007), and asymptomatic lacune (p=0.013) is associated with stroke progression. Multivariate logistic regression analysis adjusted with age>70 years, gender, atrial fibrillation smoking, and high sensitive C-reactive protein disclosed that asymptomatic lacune is an independent predictor of stroke progression after acute cerebral infarction (odds ratio=1.76, confidence interval=1.03-3.02 p-value=0.039). Conclusion: Our study showed that the presence of asymptomatic lacune is an independent imaging biomarker associated with neurological deterioration after cerebral infarction.

Background: Intracranial aneurysms (IA) are outpouches of weakened arterial walls encompassing around 3% of general population. Until now, pathophysiology of formation, growth and rupture of the aneurysm is not fully understood, but former studies have shown that intrinsic arterial wall defect contribute to the aneurysmal pathogenesis. Prevalence of IA in patients with coarctation of aorta or bicuspid aortic valve is significantly higher than general population, which suggests common pathophysiology between IA and aortopathy. However, the relationship is difficult to generalize because of the rarity of coarctation of aorta and bicuspid aortic valve. We used common echocardiographic marker, aortic root dimension (ARD), to show the association. Methods: We reviewed all patients with IA and performed echocardiography (n=260) who admitted to our institution for coil embolization or for management of ischemic stroke. Patients aged Results: Non-eccentric group had more cerebrovascular risk factors such as hypertension (p Conclusion: ARD was significantly large in eccentric group compared with non-eccentric group. In patients with IA, common intrinsic arterial wall defect exist between intracranial artery and ascending aorta, and it may be attributable to genetics or developmental process.

BACKGROUND: Cerebral arterial calcification has been reported to be associated with lacunar infarction and white matter hyperintensities. The aim of the present study was to determine the association between arterial calcification and cerebral microbleed (CMB) which is a small hemorrhagic lesion in the brain and is known to be associated with small vessel disease (SVD). METHODS: We identified 834 consecutive patients with acute ischemic stroke who visited a tertiary university hospital within 7 days of symptom onset and underwent both CT angiography and brain MR imaging. Calcifications in the intracranial internal carotid artery (ICA) were graded on CT angiography. CMBs were counted relative to their location on susceptibility-weighted imaging. The association between ICA calcification and CMB was tested using logistic regression analysis. RESULTS: The patients ranged in age from 26 to 111 years (67 ± 12.7 years, mean ± standard deviation). ICA calcification and CMB were found in 660 patients (79.1%) and 335 patients (40.2%), respectively. On multivariable analysis, ICA calcification was associated with CMB of any location (odds ratio (OR) 1.76, 95% confidence interval (CI) 1.31 - 2.36 for mild calcification; OR 2.86, 95% CI 2.01 - 4.08 for severe calcification, respectively). More robust association was found between calcification and CMB in the basal ganglia, thalamus, or brainstem (odds ratio (OR) 1.76, 95% confidence interval (CI) 1.27 - 2.44 for mild calcification; OR 3.51, 95% CI 2.39 - 5.14 for severe calcification, respectively). However, ICA calcification was not associated with CMB strictly located in the lobar area. CONCLUSIONS: ICA calcification is an independent predictor for deep CMB but not for a strictly lobar CMB. Our findings add evidence to the hypothesis that cerebral arterial calcification is associated with SVD and might contribute to the elucidation of the pathogenesis of SVD.

Background: MicroRNAs (miRNA) are short sequenced non-coding RNAs that control gene expression by post-transcriptional RNA silencing. Recent studies reported that circulating miRNA can be detected in various disease models such as cancer and myocardial infarction. In this study we examined the expression level of circulating miRNA in acute ischemic stroke patients. Methods: Between August 1st 2011 and March 31st 2012, those patients who admitted due to acute cerebral infarction were included. We determined to measure five miRNA candidates including miR-17, 21, 106a, 126, and 200b, which are related with atherosclerosis and vascular injury from previous studies. We obtained 5 ml of venous sample from each patient after informed consent and reviewed clinical variable and laboratory data. The expression level of miRNA was calculated by quantitative real-time PCR. The patients without acute stroke were compared as control. Results: Total of 108 patients was included in the study and 75 patients were diagnosed as acute ischemic stroke. Acute stroke patients showed higher level of circulating miR-17 level than control patients, which was confirmed by multiple logistic regression analysis including age, gender, systolic blood pressure, diabetes mellitus, and white blood cell count (p=0.018, odds ratio=2.149, confidence interval=1.142-4.046). The level of miR-126 was correlated with the degree of atherosclerosis on brain MR angiography (r=0.319, p=0.001). Among the stroke subtypes, cardioembolic stroke patients had lower level of miR-126 than non-cardioembolic patients (p=0.015). Conclusion: This study shows that circulating miR-17 was increased after acute ischemic stroke and miR-126 level was related to atherosclerosis. These miRNAs might serve as potential markers of cerebral infarction pathogenesis and warrants further investigation.

Background: The cessation of antithrombotic agent is related with increased thromboembolic events. However, the clinical characteristics of stroke after antithrombotics withdrawal and its impact on stroke outcome have not been studied. In this study we tried to evaluate clinical significance of antithrombotics withdrawal in stroke occurrence and outcome. Methods: Between January 1 st 2009, and March 1 st 2012, the acute stroke patients who admitted in Seoul National University Hospital within seven days after symptom onset were eligible in the study. We defined stroke after antithrombotics withdrawal (SAW) as those stroke patients who had maintained antiplatelet agent or anticoagulant regularly but ceased their medication before stroke onset. We reviewed their clinical characteristics as well as the reason of medication cessation, type of medication, and duration between medication hold and stroke onset. To evaluate the effect of antithrombotics withdrawal in stroke outcome, we compared SAW with stroke patients which occurred on regular medication. Results: Among 1635 acute stroke patients, 84 patients (5.2%) were identified as SAW during the inclusion period, with a mean age of 68.0±13.2 years including 49 male patients. The most common cause of medication cessation is poor compliance in 32 patients (37.7%), followed by pre-operation/procedure hold in 24, antithrombotics complication in 16, and doctor’s decision in 13. The 42 patients with SAW who had stroke within one month after medication cessation were compared with 261 patients who experienced cerebral infarction during regular medication. Stroke progression defined as 3 or more NIHSS worsening during admission was more prevalent in SAW patients than in patients with regular medication (14.3% vs. 5.0%, p=0.042). The patients with poor functional outcome defined as mRS of 5 and 6 at discharge were more common in SAW than in patients with regular medication (16.7% vs. 6.5%, p=0.043). Conclusion: This study shows that 5.2% of total stroke is due to medication withdrawal, and poor compliance is the most common cause of antithrombotics hold. Stroke after antithrombotics hold is associated with higher rate of stroke progression and poor outcome, implying exacerbated thromboembolic state.

Background and Purpose— Understanding on distinct subsets of endothelial progenitor cells may provide insights of endothelial dysfunction or repair in the acute ischemic event. Recent in vitro data have reported the colony-forming unit (CFU) and outgrowth cell population as a subset of endothelial progenitor cells. In this study, we undertook to validate the significance of CFU number and outgrowth cell yield in acute stroke. Methods— Mononuclear cells were isolated from the peripheral blood of 75 patients with acute stroke, 45 patients with chronic stroke, and 40 age-matched healthy volunteers. CFU numbers were counted after culturing them for 7 days, and outgrowth cell appearance was measured during the 2 months of culture. Endothelial progenitor cell function was also evaluated by matrigel plate assays. Independent parameters predicting CFU number and outgrowth cell yield were assessed using logistic regression analysis. Results— The CFU numbers and tube formation abilities in matrigel assays were significantly reduced in patients with acute stroke compared with patients with chronic stroke or healthy control subjects. Moreover, patients with large artery atherosclerosis had much lower CFU numbers and functional activities than ones with cardioembolism. Outgrowth cells were isolated from 10% of healthy control subjects and 22% of patients with chronic stroke during the cultures, but from 71% of patients with stroke. Multivariate analysis identified glycosylated hemoglobin and National Institutes of Health Stroke Scale on admission as significant independent predictors of a low CFU number and a high isolation frequency of outgrowth cells, respectively. Conclusion— CFU number may thus represent an accumulated endothelial progenitor cell dysfunctional status, whereas outgrowth cell appearance may reflect the resilience of the systemic circulation to acute ischemic stress.

Background and Purpose— Astrocytic glutamate transporter protein, GLT-1 (EAAT2), recovers extracellular glutamate and ensures that neurons are protected from excess stimulation. Recently, β-lactam antibiotics, like ceftriaxone (CTX), were reported to induce the upregulation of GLT-1. Here, we investigated ischemic tolerance induction by CTX in an experimental model of focal cerebral ischemia. Methods— CTX (200 mg/kg per day, IP) was administered for 5 consecutive days before transient focal ischemia, which was induced by intraluminal thread occlusion of the middle cerebral artery for 90 minutes or permanently. Results— Repeated CTX injections enhanced GLT-1 mRNA and protein expressions after 3 and 5 days of treatment, respectively. CTX-pretreated animals showed a reduction in infarct volume by 58% (reperfusion) and 39% (permanent), compared with the vehicle-pretreated animals at 24 hours postischemia ( P P P Conclusions— This study presents evidence that CTX induces ischemic tolerance in focal cerebral ischemia and that this is mediated by GLT-1 upregulation.

Background and Purpose— The rate of nitric oxide (NO) generation from nitrite is linearly dependent on reductions in oxygen and pH levels. Recently, nitrite-derived NO has been reported to exert a profound protection against liver and heart ischemia-reperfusion injury. In this study, we hypothesized that nitrite would be reduced to NO in the ischemic brain and exert NO-dependent neuroprotective effects. Methods— Cerebral ischemia-reperfusion injury was induced by intraluminal thread occlusion of middle cerebral artery in the adult male rats. Solutions of sodium nitrite were infused intravenously at the time of reperfusion. Sodium nitrate and carboxy-PTIO (30 minutes before ischemic surgery), a direct NO scavenger, were infused for comparisons. Results— Nitrite reduced infarction volume and enhanced local cerebral blood flow and functional recovery. The effects were observed at concentrations of 48 nmol and 480 nmol, but not at 4800 nmol nitrite and 480 nmol nitrate. The neuroprotective effects of nitrite were inhibited completely by the carboxy-PTIO. The 480 nmol nitrite attenuated dihydroethidium activity, 3-nitrotyrosine formation, and lipid peroxidation in the ischemic brain. Conclusions— Nitrite exerted profound neuroprotective effects with antioxidant properties in the ischemic brains. These results suggest that nitrite, as a biological storage reserve of NO, may be a novel therapeutic agent in the setting of acute stroke.