Impact of Slow Blood Filling via Collaterals on Infarct Growth: Comparison of Mismatch and Collateral Status / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Perfusion-diffusion mismatch has been evaluated to determine whether the presence of a target mismatch helps to identify patients who respond favorably to recanalization therapies. We compared the impact on infarct growth of collateral status and the presence of a penumbra, using magnetic resonance perfusion (MRP) techniques. METHODS: Consecutive patients who were candidates for recanalization therapy and underwent serial diffusion-weighted imaging (DWI) and MRP were enrolled. A collateral flow map derived from MRP source data was generated by automatic post-processing. The impact of a target mismatch (Tmax>6 s/apparent diffusion coefficient (ADC) volume≥1.8, ADC volume10 s for ADC volume<100 mL) on infarct growth was compared with MR-based collateral grading on day 7 DWI, using multivariate linear regression analysis. RESULTS: Among 73 patients, 55 (75%) showed a target mismatch, whereas collaterals were poor in 14 (19.2%), intermediate in 36 (49.3%), and good in 23 (31.5%) patients. After adjusting for initial severity of stroke, early recanalization (P<0.001) and the MR-based collateral grading (P=0.001), but not the presence of a target mismatch, were independently associated with infarct growth. Even in patients with a target mismatch and successful recanalization, the degree of infarct growth depended on the collateral status. Perfusion status at later Tmax time points (beyond the arterial phase) was more closely correlated with collateral status. CONCLUSIONS: Patients with good collaterals show a favorable outcome in terms of infarct growth, regardless of the presence of a target mismatch pattern. The presence of slow blood filling predicts collateral status and infarct growth.

Association of Left Atrial Enlargement with Cortical Infarction in Subjects with Patent Foramen Ovale / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Left atrial dysfunction has been reported in patients with patent foramen ovale (PFO). Here we investigated the role of left atrial dysfunction in the development of embolic stroke in patients with PFO. METHODS: We identified consecutive patients with embolic stroke of undetermined sources except for PFO (PFO+ESUS). Healthy subjects with PFO served as controls (PFO+control). A stratified analysis by 10-year age group and an age- and sex- matching analysis were performed to compare echocardiographic markers between groups. In the PFO+ESUS group, infarct patterns of PFO-related stroke were determined (cortical vs. cortico-subcortical) and analyzed in correlation with left atrial function parameters. RESULTS: A total of 118 patients and 231 controls were included. The left atrial volume indices (LAVIs) of the PFO+ESUS patients were higher than those of the PFO+controls in age groups of 40–49, 50–59, and 60–69 years (P28 mL/m2) LAVI was more associated with the cortical infarct pattern (P=0.043 for an acute infarction and P=0.024 for a chronic infarction, both adjusted for age and shunt amount). The degree of right-to-left shunting was not associated with infarct patterns, but with the posterior location of acute infarcts (P=0.028). CONCLUSIONS: Left atrial enlargement was associated with embolic stroke in subjects with PFO. Left atrial physiology might contribute to the development of PFO-related stroke and need to be taken into consideration for optimal prevention of PFO-related stroke.

Lack of Association of Clinical Factors (SAMe-TT2R2) with CYP2C9/VKORC1 Genotype and Anticoagulation Control Quality / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Advantages of new oral anticoagulations may be greater in atrial fibrillation (AF) patients of poor anticoagulation control with warfarin. The SAMe-TT2R2 scoring system, based on clinical variables, was recently developed to aid in identifying these patients. In this study, we investigated the association of this clinical composite score with genetic factors related warfarin dosing and the quality of anticoagulation control. METHODS: Clinical and genetic data were collected from 380 consecutive Korean patients with AF (CHA2DS2-VASc score, 3.5+/-1.8) who were followed for an average of 4 years. We evaluated factors associated with time in therapeutic range (TTR, INR 2-3), including the CYP2C9 and VKORC1 genotypes and the SAMe-TT2R2 score (Sex female, Age two co-morbidities], Treatment [interacting drugs, e.g., amiodarone], Tobacco use within 2 years [doubled], and Race non-white [doubled]). RESULTS: The average SAMe-TT2R2 score was 3.4+/-0.9, range 2-7; and 153 patients (40.2%) had SAMe-TT2R2 scores > or =4. Time in specific INR ranges varied depending on the VKORC1 genotype but not with the CYP2C9 genotype or the SAMe-TT2R2 score. TTR was higher in patients with the VKORC1 1173C>T than in VKORC1 TT (61.7+/-16% vs. 56.7+/-17.4%, P=0.031). Multivariate testing showed that VKORC1 genotype but not the SAMe-TT2R2 score was significantly associated with labile INRs. There was no correlation between the SAMe-TT2R2 scores and pharmacogenetic data. CONCLUSIONS: A genetic factor, but none of the common clinical and demographic factors, as combined in the SAMe-TT2R2 score, was associated with the quality of anticoagulation control in Korean patients with AF.

Patent Foramen Ovale and Stroke-Current Status / 대한뇌졸중학회지

Patent foramen ovale (PFO) is growing in clinical interest because of a renewed focus on embolic stroke of undetermined source (ESUS), the PFO attributable fraction (the 10-point Risk of Paradoxical Embolism score), technical advances in PFO diagnosis, and the emergence of endovascular device closure as a treatment option. However, recent randomized controlled trials of the management of patients with ESUS and PFO failed to demonstrate the superiority of closure over medical treatment. The mechanisms of stroke other than paradoxical embolism may be important in patients with ESUS and PFO. This paper reviews the current understanding of the pathophysiology of stroke and therapeutic options in patients with PFO and ESUS.

Antioxidant Effects of Statins in Patients with Atherosclerotic Cerebrovascular Disease

BACKGROUND AND PURPOSE: Oxidative stress is involved in the pathophysiological mechanisms of stroke (e.g., atherosclerosis) and brain injury after ischemic stroke. Statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, have both pleiotropic and low-density lipoprotein (LDL)-lowering properties. Recent trials have shown that high-dose statins reduce the risk of cerebrovascular events. However, there is a paucity of data regarding the changes in the oxidative stress markers in patients with atherosclerotic stroke after statin use. This study evaluated changes in oxidative stress markers after short-term use of a high-dose statin in patients with atherosclerotic stroke. METHODS: Rosuvastatin was administered at a dose of 20 mg/day to 99 patients who had suffered an atherosclerotic stroke and no prior statin use. Blood samples were collected before and 1 month after dosing, and the serum levels of four oxidative stress markers-malondialdehyde (MDA), oxidized LDL (oxLDL), protein carbonyl content (PCO), and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-were evaluated to determine the oxidation of MDA and lipids, proteins, and DNA, respectively, at both of those time points. RESULTS: The baseline levels and the degrees of reduction after statin use differed among the oxidative stress markers measured. MDA and PCO levels were associated with infarct volumes on diffusion-weighted imaging (r=0.551, p<0.05, and r=0.444, p=0.05, respectively). Statin use decreased MDA and oxLDL levels (both p<0.05) but not the PCO or 8-OHdG level. While the reduction in MDA levels after statin use was not associated with changes in cholesterol, that in oxLDL levels was proportional to the reductions in cholesterol (r=0.479, p<0.01), LDL (r=0.459, p<0.01), and apolipoprotein B (r=0.444, p<0.05). CONCLUSIONS: The impact of individual oxidative stress markers differs with time after ischemic stroke, suggesting that different oxidative markers reflect different aspects of oxidative stress. In addition, short-term use of a statin exerts antioxidant effects against lipid peroxidation via lipid-lowering-dependent and -independent mechanisms, but not against protein or DNA oxidation in atherosclerotic stroke patients.

An Adult Moyamoya Disease Confirmed by Ring Finger Protein 213 Gene Test and Radiological Studies

A 63-year-old female complained of transient dysarthria. MRA was conducted to evaluate this symptom, revealing distal internal carotid artery occlusion with collateral vessel development, suggesting Moyamoya disease, which had not been detected in MRA performed 5 years previously. Vascular risk factors and laboratory findings suggested no cardiac or autoimmune diseases. The diameter of stenosis of the middle cerebral artery on high-resolution MRI was 2.11 mm, and genetic evaluation revealed mutation of the gene encoding ring finger protein 213 (RNF213). High-resolution MRI and gene studies are useful for distinguishing between Moyamoya disease and atherosclerosis.

Biomarkers for Stroke / 대한뇌졸중학회지

BACKGROUND: Major stroke clinical trials have failed during the past decades. The failures suggest the presence of heterogeneity among stroke patients. Biomarkers refer to indicators found in the blood, other body fluids or tissues that predicts physiologic or disease states, increased disease risk, or pharmacologic responses to a therapeutic intervention. Stroke biomarkers could be used as a guiding tool for more effective personalized therapy. MAIN CONTENTS: Three aspects of stroke biomarkers are explored in detail. First, the possible role of biomarkers in patients with stroke is discussed. Second, the limitations of conventional biomarkers (especially protein biomarkers) in the area of stroke research are presented with the reasons. Lastly, various types of biomarkers including traditional and novel genetic, microvesicle, and metabolomics-associated biomarkers are introduced with their advantages and disadvantages. We especially focus on the importance of comprehensive approaches using a variety of stroke biomarkers. CONCLUSION: Although biomarkers are not recommended in practice guidelines for use in the diagnosis or treatment of stroke, many efforts have been made to overcome the limitations of biomarkers. The studies reviewed herein suggest that comprehensive analysis of different types of stroke biomarkers will improve the understanding of individual pathophysiologies and further promote the development of screening tools for of high-risk patients, and predicting models of stroke outcome and rational stroke therapy tailored to the characteristics of each case.

Primary Angiitis of the Central Nervous System Diagnosed by High-Resolution Vessel Wall MRI

Primary angiitis of the central nervous system (PACNS) is a poorly understood form of vascular inflammatory disease that is restricted to the brain and spinal cord. A 38-year-old woman presented with severe headache and transient aphasia. Her cerebrospinal fluid exhibited aseptic meningitis, and high-resolution vessel-wall MRI (HRVW-MRI) revealed narrowing of multiple intracranial vessels with concentric wall thickening and diffuse enhancement, suggestive of PACNS. High-dose steroid and azathioprine therapy resulted in a significant improvement in vessel wall thickening, and enhancement was observed on the follow-up HRVW-MRI.

Ischemic Stroke in Takayasu's Arteritis: Lesion Patterns and Possible Mechanisms

BACKGROUND AND PURPOSE: The purpose of the present study was to use brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) to identify the mechanism of stroke in patients with Takayasu's arteritis (TA). METHODS: Among a retrospective cohort of 190 TA patients, 21 (3 males and 18 females) with a mean age of 39.9 years (range 15-68 years) who had acute cerebral infarctions were included in lesion pattern analyses. The patients' characteristics were reviewed, and infarction patterns and the degree of cerebral artery stenosis were evaluated. Ischemic lesions were categorized into five subgroups: cortical border-zone, internal border-zone, large lobar, large deep, and small subcortical infarctions. RESULTS: In total, 21 ischemic stroke events with relevant ischemic lesions on MRI were observed. The frequencies of the lesion types were as follows: large lobar (n=7, 33.3%), cortical border zone (n=6, 28.6%), internal border zone (n=1, 4.8%), small cortical (n=0, 0%), and large deep (n=7, 33.3%). MRA revealed that 11 patients had intracranial artery stenosis. CONCLUSIONS: Hemodynamic compromise in large-artery stenosis and thromboembolic mechanisms play significant roles in ischemic stroke associated with TA.

Benign Oligemia Despite a Malignant MRI Profile in Acute Ischemic Stroke

BACKGROUND: It has recently been suggested that diffusion and perfusion MRI can identify subgroups likely to benefit or potentially be harmed by reperfusion therapies. CASE REPORT: We investigated serial MRI data of two patients with occlusion of the proximal middle cerebral artery (MCA). In both cases, acute multiple cortical infarcts evident on diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) showed extensive areas of severe perfusion delays, indicating a malignant MRI profile. However, despite the malignant MRI profiles in these cases, no new ischemic lesions or hemorrhage evolved even in the presence of persistent arterial occlusion, and the patients recovered without sequelae. CONCLUSIONS: These two cases suggest that time-domain PWI findings should be interpreted with caution in certain scenarios of acute ischemic stroke.

Paroxysmal Horizontal Diplopia Related to Brainstem Lesion

Paroxysmal diplopia and dysarthria-ataxia have been reported in multiple sclerosis, stroke and Behcet's disease. We present a case of 25-year-old man with multiple brain lesions, who developed paroxysmal horizontal dysconjugate eyeball deviation, dysarthria and ataxia. Subtraction ictal SPECT co-registered to MR images demonstrated hyperperfusion in the brainstem and cerebellum during the paroxysms.

Prevalence Rate and Risk Factors of Dementia Compared between Urban and Rural Communities of the Metropolitan Kwangju Area / 신경정신의학

OBJECTIVES: The purpose of this study was to investigate the prevalence rate and risk factors of dementia in an urban and a rural sample of older persons in the metropolitan Kwangju area, Republic of Korea. In addition, the prevalence rate and risk factors of dementia between the two samples were compared. METHODS: A two-phase epidemiological study of residents aged 65 or over(N=1,598) was conducted in a highly developed, urban and a non-contiguous, poorly developed, rural area of metropolitan Kwangju. In the first(screening) phase, 38 trained research assistants collectively performed in-home interviews for all participants. Detailed sociodemographic characteristics were gathered and the Korean version of Mini-Mental State Examination(MMSE-K) was administered. In the second(diagnosing) phase, diagnosis of dementia was established for those scoring 24 or less on the MMSE-K in the screening phase(N=431), and etiological types of dementia were classified to Alzheimer's disease (AD), vascular dementia(VaD) or miscellanous type by two teams of experts. Prevalence rate of dementia was determined in the participants, and age-standardized prevalence rate adjusted by age distribution in metropolitan Kwangju was estimated. For AD, the risk factors were investigated in all participants, and analyses were repeated for the urban and rural samples separately. RESULTS: The participating rates in the first and second phases were 71.0%(N=1,134) and 83.2% (N=410), respectively. In the participants, the prevalence rates of dementia(all types), AD and VaD were 9.7%, 5.2% and 1.8%, respectively. The age-standardized prevalence rates were 10.7%, 5.7% and 1.9%, respectively. Aging, female gender and no education(complete lack of formal education) were identified as independent risk factors for AD. No difference between the urban and rural samples was observed in the prevalence rates of dementia(all types), AD and VaD. However, risk factors for AD differed between these areas. In the urban sample, no education was the only significant factor; whereas, aging and female gender were identified as risk factors in the rural sample. CONCLUSION: A high prevalence rate of dementia was observed among old persons in metropolitan Kwangju, consistent with previous studies conducted in other Korean areas. The risk factor profiles for AD differed between urban and rural settings. The results of this study reflect the current status of dementia in Korea and suggests that appropriate management and prevention strategies for dementia should be tailored toward the geographic settings.