Hyun-Wook Nah

Risk Factors and Stroke Mechanisms in Atherosclerotic Stroke Intracranial Compared With Extracranial and Anterior Compared With Posterior Circulation Disease

Background and Purpose— The aim of this study was to investigate differences in risk factors and stroke mechanisms between intracranial atherosclerosis (ICAS) and extracranial atherosclerosis (ECAS) and between anterior and posterior circulation atherosclerosis. Methods— A multicenter, prospective, Web-based registry was performed on atherosclerotic strokes using diffusionweighted magnetic resonance imaging and magnetic resonance angiography. Stroke mechanisms were categorized as artery-to-artery embolism, in situ thrombo-occlusion, local branch occlusion, or hemodynamic impairment. Results— Onethousand patients were enrolled from 9 university hospitals. Age (odds ratio [OR], 1.033; 95% confidence interval [CI], 1.018–1.049), male gender (OR, 3.399; 95% CI, 2.335–4.949), and hyperlipidemia (OR, 1.502; 95% CI, 1.117–2.018) were factors favoring ECAS (vs ICAS), whereas hypertension (OR, 1.826; 95% CI, 1.274–2.618; P=0.001) and diabetes mellitus (OR, 1.490; 95% CI, 1.105–2.010; P=0.009) were related to posterior (vs anterior) circulation diseases. Metabolic syndrome was a factor related to ICAS (vs ECAS) only in posterior circulation strokes (OR, 2.433; 95% CI, 1.005–5.890; P=0.007). Stroke mechanisms included arterytoartery embolism (59.7%), local branch occlusion (14.9%), in situ thrombo-occlusion (13.7%), hemodynamic impairment (0.9%), and mixed (10.8%). Anterior ICAS was more often associated with artery-to-artery embolism (51.8% vs 34.0%) and less often associated with local branch occlusion (12.3% vs 40.4%) than posterior ICAS (P<0.001). Conclusions— The prevalence of risk factors and stroke mechanisms differ between ICAS and ECAS, and between anterior and posterior circulation atherosclerosis. Posterior ICAS seems to be closely associated with metabolic derangement and local branch occlusion. Prevention and management strategies may have to consider these differences.

Efficacy and Safety of Combination Antiplatelet Therapies in Patients With Symptomatic Intracranial Atherosclerotic Stenosis

Background and Purpose— An optimal strategy for management of symptomatic intracranial atherosclerotic stenosis (ICAS) has not yet been established. We compared the efficacy of 2 combinations of antiplatelets, aspirin plus cilostazol (cilostazol group) verus aspirin plus clopidogrel (clopidogrel group), on the progression of ICAS, which is known to be associated with clinical stroke recurrence. Methods— In this investigator-initiated double-blind trial, 457 patients with acute symptomatic stenosis in the M1 segment of the middle cerebral artery or the basilar artery were randomly allocated into either a cilostazol group or a clopidogrel group. After 7 months of treatment, follow-up MR angiogram and MRI were performed. The primary end point was the progression of ICAS in comparison with stenosis on the baseline MR angiogram. Secondary end points included the occurrence of new ischemic lesions on MRI, composite of cardiovascular events, and major bleeding complications. Results— Cardiovascular events occurred in 15 of 232 patients (6.4%) in the cilostazol group and 10 of 225 (4.4%) in the clopidogrel group (P=0.312). Cilostazol did not reduce the progression of symptomatic ICAS (20 of 202) compared to clopidogrel (32 of 207) (odds ratio, 0.61; P=0.092), although favorable changes in serum lipoproteins were observed in the cilostazol group. There were no significant differences between the 2 groups with respect to new ischemic lesions (18.7% versus 12.0%; P=0.078) and major hemorrhagic complications (0.9% versus 2.6%; P=0.163). Conclusions— This trial failed to show significant difference in preventing progression of ICAS and new ischemic lesions between the 2 combination antiplatelet therapies in the patients with symptomatic ICAS. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00130039.

New Cerebral Lesions on T2*-Weighted Gradient-Echo Imaging after Cardiac Valve Surgery

Background: It is well known that silent ischemic brain lesions on diffusion-weighted imaging (DWI) commonly occur after various interventional procedures or surgeries. However, to our knowledge, postoperative new lesions on T2*-weighted gradient-echo imaging (GRE) have never been explored. Methods: This prospective observational study enrolled 19 consecutive patients undergoing cardiac valve surgery. Preoperative and postoperative (within 7 days) GRE and DWI were performed. New GRE lesions were defined as signal loss lesions on postoperative GRE which were not observed on preoperative GRE. Long-term follow-up GRE was performed in a limited number of cases. Results: Twelve patients developed 26 small (<10 mm) new GRE lesions. Of these patients, 1 had a generalized seizure accompanied by confusion and facial weakness with DWI lesions, and 1 showed confusion of short duration without DWI lesions. Long-term follow-up GRE was performed 3 years after surgery in 4 patients. Of the 12 new GRE lesions in these 4 patients, 11 lesions were still observable on long-term follow-up GRE. Conclusions: New cerebral lesions on GRE after cardiac valve surgery are common and are presumed to be rapidly developed microbleeds and mostly asymptomatic. Further studies are needed to investigate the precise nature and clinical implications of new GRE lesions.

Moyamoya Disease-Related Versus Primary Intracerebral

Background and Purpose— The purpose of our study was to compare lesion location between moyamoya disease-related intracerebral hemorrhage (MMD-ICH) and primary intracerebral hemorrhage (P-ICH). Methods— Ninety-three patients each with MMD-ICH and P-ICH were compared. In patients with MMD-ICH, angiographic findings were assessed with special attention to the prominent anterior choroidal artery. Follow-up data were obtained through clinical visit and telephone interview. Results— The location of hemorrhage was different between MMD-ICH and P-ICH, the most frequent one being intraventricular region (37.6%) in the former and putaminal region (46.2%) in the latter (P<0.001). Intraventricular hemorrhage was more frequent in MMD-ICH than P-ICH (80.6% versus 20.4%, P<0.001). In MMD-ICH, primary intraventricular hemorrhage was more closely associated with prominent ipsilateral anterior choroidal artery than ICHs without intraventricular hemorrhage (75.0% versus 16.7%, P<0.001). Higher rates of rebleeding and infarction were observed in MMD-ICH than in age- and sex-matched patients with P-ICH. Conclusions— MMD-ICH may differ from P-ICH in hemorrhage location, generally presenting with intraventricular hemorrhage with or without ICH, which may be due to a prominent anterior choroidal artery. Patients with MMD may be more likely to experience recurrent bleeding and infarction.

Diagnostic and Prognostic Value of Multimodal MRI in Transient Ischemic Attack

Background The clinical diagnosis of transient ischemic attack is highly subjective, and the risk prediction after transient ischemic attack using the clinical parameters still remains unsatisfactory. Aims We aimed to investigate the diagnostic and prognostic value of multimodal magnetic resonance imaging in transient ischemic attack patients. Methods We prospectively performed diffusion-weighted imaging, perfusion-weighted imaging, and intracranial and extracranial magnetic resonance angiogram within 72 h of symptom onset in 162 transient ischemic attack patients defined by the classical time-based definition. Follow-up diffusion-weighted imaging was obtained three-days later in patients who did not exhibit lesions on the initial diffusion-weighted imaging. The occurrence of clinical events (transient ischemic attack or stroke) three-months after the initial transient ischemic attack was recorded, and the ABCD2 and ABCD3-I scores were calculated. The clinical and imaging parameters were compared between patients with and without initial diffusion-weighted imaging lesion, clinical events, and follow-up diffusion-weighted imaging lesions. Results Abnormalities were present on diffusion-weighted imaging, perfusion-weighted imaging, and magnetic resonance angiogram in 38·9%, 44·1%, and 51·9% of patients, respectively. Diffusion-weighted imaging plus perfusion-weighted imaging explained 64·8%, and the addition of magnetic resonance angiogram explained 74% of the transient ischemic attack symptoms. The initial diffusion-weighted imaging positivity was associated with longer time from symptom onset to magnetic resonance imaging examination (odds ratio, 1·039; 95% confidence interval, 1·008–1·071; P = 0·013). On follow-up diffusion-weighted imaging, new lesions were found in 46·7% of the patients who initially showed normal diffusion-weighted imaging findings. Initial perfusion-weighted imaging abnormality predicted the appearance of follow-up diffusion-weighted imaging lesion (chi-square = 7·774, P = 0·005). During the three-months follow-up, 23 patients (14·2%) experienced subsequent transient ischemic attack (n = 16) or stroke (n = 7). Symptomatic magnetic resonance angiogram abnormality (odds ratio, 12·667; 95% confidence interval, 2·859–56·110; P = 0·001) was the only independent factor associated with clinical events with a sensitivity of 91·3% and specificity of 54·7% (C statistics, 0·73). None with initially normal multimodal magnetic resonance imaging findings developed subsequent clinical events. Conclusions Approximately three-quarter of transient ischemic attack is associated with multimodal magnetic resonance imaging abnormality. Initial perfusion-weighted imaging abnormality predicts newly developed diffusion-weighted imaging lesions, and symptomatic magnetic resonance angiogram abnormality seems to be the most important predictor for subsequent clinical events. Multimodal magnetic resonance imaging appears to be useful in assessing transient ischemic attack and predicting outcome in these patients.

Predictive Value of Pulse Pressure in Acute Ischemic Stroke for Future Major Vascular Events

Background and Purpose— This study aimed to investigate whether pulse pressure (PP) obtained during the acute stage of ischemic stroke can be used as a predictor for future major vascular events. Methods— Using a multicenter prospective stroke registry database, patients who were hospitalized for ischemic stroke within 48 hours of onset were enrolled in this study. We analyzed blood pressure (BP) data measured during the first 3 days from onset. Primary and secondary outcomes were time to a composite of stroke recurrence, myocardial infarction, all-cause death, and time to stroke recurrence, respectively. Results— Of 9840 patients, 4.3% experienced stroke recurrence, 0.2% myocardial infarction, and 7.3% death during a 1-year follow-up period. In Cox proportional hazards models including both linear and quadratic terms of PP, PP had a nonlinear J-shaped relationship with primary (for a quadratic term of PP, P=0.004) and secondary (P<0.001) outcomes. The overall effects of PP and other BP parameters on primary and secondary outcomes were also significant (P<0.05). When predictive power of BP parameters was compared using a statistic of −2 log-likelihood differences, PP was a stronger predictor than systolic BP (8.49 versus 5.91; 6.32 versus 4.56), diastolic BP (11.42 versus 11.05; 10.07 versus 4.56), and mean atrial pressure (8.75 versus 5.91; 7.03 versus 4.56) for the primary and secondary outcomes, respectively. Conclusions— Our study shows that PP when measured in the acute period of ischemic stroke has nonlinear J-shaped relationships with major vascular events and stroke recurrence, and may have a stronger predictive power than other commonly used BP parameters.

Patient Selection and Clinical Efficacy of Urgent Superficial Temporal Artery-Middle Cerebral Artery Bypass in Acute Ischemic Stroke Using Advanced Magnetic Resonance Imaging Techniques

BACKGROUNDnSelected patients with acute ischemic stroke might benefit from superficial temporal artery-middle cerebral artery (STA-MCA) bypass, but the indications for urgent STA-MCA bypass are unknown.nnnOBJECTIVEnTo report our experiences of urgent STA-MCA bypass in patients requiring urgent reperfusion who were ineligible for other reperfusion therapies, using advanced magnetic resonance imaging (MRI) techniques.nnnMETHODSnThe inclusion criteria for urgent STA-MCA bypass were as follows: acute infarct volume <70u2009mL with a ratio of perfusion/diffusion lesion volume ≥1.2, and a regional cerebral blood volume ratio >0.85. From January 2013 to October 2015, 21 urgent STA-MCA bypass surgeries were performed. The control group included 19 patients who did not undergo bypass surgery mainly due to refusal of surgery or the decision of the neurologist. Clinical and radiological data were compared between the surgery and control group.nnnRESULTSnThe median age of the control group (70 years, interquartile range [IQR] 58-76) was higher than that of the surgery group (62 years, IQR 49-66), but the median preoperative diffusion and perfusion lesion volumes of the surgery group (13.8u2009mL, IQR 7.5-26.0 and 120.9u2009mL, IQR 84.9-176.0, respectively) were higher than those of the control group (5.6u2009mL, IQR 2.1-9.1 and 69.7u2009mL, IQR 23.9-125.3, respectively). Sixteen (76.2%) patients in the surgery group and 2 (10.5%) patients in the control group had favorable outcomes ( P < .001). Logistic regression analysis identified bypass surgery as the strongest predictive factor.nnnCONCLUSIONnSTA-MCA bypass can be used as a therapeutic tool for acute ischemic stroke. Advanced MRI techniques are helpful for selecting patients and for decision making.

One-Year Outcomes After Minor Stroke or High-Risk Transient Ischemic Attack: Korean Multicenter Stroke Registry Analysis

Background and Purpose— Patients with minor ischemic stroke or transient ischemic attack are at high risk of recurrent stroke and vascular events, which are potentially disabling or fatal. This study aimed to evaluate contemporary subsequent vascular event risk after minor ischemic stroke or transient ischemic attack in Korea. Methods— Patients with minor ischemic stroke or high-risk transient ischemic attack admitted within 7 days of symptom onset were identified from a Korean multicenter stroke registry database. We estimated 3-month and 1-year event rates of the primary outcome (composite of stroke recurrence, myocardial infarction, or all-cause death), stroke recurrence, a major vascular event (composite of stroke recurrence, myocardial infarction, or vascular death), and all-cause death and explored differences in clinical characteristics and event rates according to antithrombotic strategies at discharge. Results— Of 9506 patients enrolled in this study, 93.8% underwent angiographic assessment and 72.7% underwent cardiac evaluations; 25.1% had symptomatic stenosis or occlusion of intracranial arteries. At discharge, 95.2% of patients received antithrombotics (antiplatelet polytherapy, 37.1%; anticoagulation, 15.3%) and 86.2% received statins. The 3-month cumulative event rate was 5.9% for the primary outcome, 4.3% for stroke recurrence, 4.6% for a major vascular event, and 2.0% for all-cause death. Corresponding values at 1 year were 9.3%, 6.1%, 6.7%, and 4.1%, respectively. Patients receiving nonaspirin antithrombotic strategies or no antithrombotic agent had higher baseline risk profiles and at least 1.5× higher event rates for clinical event outcomes than those with aspirin monotherapy. Conclusions— Contemporary secondary stroke prevention strategies based on thorough diagnostic evaluation may contribute to the low subsequent vascular event rates observed in real-world clinical practice in Korea.

Association between Left Ventricular Dysfunction and Functional Outcomes at Three Months in Acute Ischemic Stroke

BACKGROUNDnLeft ventricular dysfunction (LVD) was associated with stroke occurrence and mortality. However, few studies have published the impact of LVD on functional stroke outcomes in the acute stroke period.nnnMETHODSnWe enrolled 1554 patients who were admitted to Dong-A University Hospital between January 2011 and November 2014. To determine the functional outcomes, the modified Rankin Scale (mRS) score at 3 months after stroke was used. The severity of LVD was defined depending on ejection fraction (EF): (1) severe (EFu2009≤u200940%); (2) mild (40%u2009<u2009EFu2009<u200955%); and (3) normal (EFu2009≥u200955%). EF was measured using transthoracic two-dimensional echocardiography. The distribution of mRS scores at 3 months after stroke was presented using LVD. Multivariable analysis was performed to predict poor functional outcomes.nnnRESULTSnOf the 1554 patients, 1417 had normal LV function, 87 had mild LVD, and 50 had severe LVD. Patients with LVD were older and had a high incidence of diabetes mellitus, atrial fibrillation, coronary artery disease, and severe stroke symptoms. With respect to treatment, patients with LVD received more thrombolysis and more anticoagulation medication after stroke. Stroke-related disability at discharge and at 3 months was significantly associated with LVD. In the multivariable analyses, old age, diabetes mellitus, high initial National Institutes of Health Stroke Scale score, stroke mechanism, and LVD were independent predictors of poor functional outcomes at 3 months.nnnCONCLUSIONSnLVD is associated with poor functional outcomes after acute ischemic stroke.

Simple Estimates of Symptomatic Intracranial Hemorrhage Risk and Outcome after Intravenous Thrombolysis Using Age and Stroke Severity

Hye Jung Lee, Ji Sung Lee, Jay Chol Choi, Yong-Jin Cho, Beom Joon Kim, Hee-Joon Bae, Dong-Eog Kim, Wi-Sun Ryu, Jae-Kwan Cha, Dae Hyun Kim, Hyun-Wook Nah, Kang-Ho Choi, Joon-Tae Kim, Man-Seok Park, Jeong-Ho Hong, Sung Il Sohn, Kyusik Kang, Jong-Moo Park, Wook-Joo Kim, Jun Lee, Dong-Ick Shin, Min-Ju Yeo, Kyung Bok Lee, Jae Guk Kim, Soo Joo Lee, Byung-Chul Lee, Mi Sun Oh, Kyung-Ho Yu, Tai Hwan Park, Juneyoung Lee, Keun-Sik Hong Department of Neurology, Ilsan Paik Hospital, Inje University, Goyang, Korea Clinical Research Center, Asan Medical Center, Seoul, Korea Department of Neurology, Jeju National University, Jeju, Korea Department of Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea Department of Neurology, Dongguk University Ilsan Hospital, Goyang, Korea Department of Neurology, Dong-A University College of Medicine, Busan, Korea Department of Neurology, Chonnam National University Medical School and Hospital, Gwangju, Korea Department of Neurology, Keimyung University Dongsan Medical Center, Daegu, Korea Department of Neurology, Eulji General Hospital, Eulji University, Seoul, Korea Department of Neurology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea Department of Neurology, Yeungnam University Hospital, Daegu, Korea Department of Neurology, Chungbuk National University Hospital, Cheongju, Korea Department of Neurology, Soonchunhyang University College of Medicine, Seoul, Korea Department of Neurology, Eulji University Hospital, Daejeon, Korea Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, Korea Department of Neurology, Seoul Medical Center, Seoul, Korea Department of Biostatistics, Korea University College of Medicine, Seoul, Korea