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Heritability of stroke is assumed not to be low, especially in the young-age stroke population. However, most genetic studies have been performed in highly selected patients with typical clinical or neuroimaging characteristics. We investigated the prevalence of 15 Mendelian stroke genes and explored the relationships between variants and the clinical and neuroimaging characteristics in a large, unselected, young stroke population.We enrolled patients aged ≤55 years with stroke or transient ischemic attack from a prospective, nationwide, multicenter stroke registry. We identified clinically relevant genetic variants (CRGV) in 15 Mendelian stroke genes (GLA, NOTCH3, HTRA1, RNF213, ACVRL1, ENG, CBS, TREX1, ABCC6, COL4A1, FBN1, NF1, COL3A1, MT-TL1, and APP) using a customized, targeted next-generation sequencing panel.Among 1,033 patients, 131 (12.7%) had 28 CRGV, most frequently in RNF213 (n=59), followed by ABCC6 (n=53) and NOTCH3 (n=15). The frequency of CRGV differed by ischemic stroke subtypes (p0.01)-highest in other determined etiology (20.1%), followed by large artery atherosclerosis (13.6%). It also differed between patients aged ≤35 years and those aged 51-55 years (17.1% vs. 9.3%, p=0.02). Only 27.1% and 26.7% of patients with RNF213 and NOTCH3 variants had typical neuroimaging features of the corresponding disorders, respectively. Variants of uncertain significance (VUS) were found in 15.4% patients.CRGV in 15 Mendelian stroke genes may not be uncommon in the young stroke population. The majority of patients with CRGV did not have typical features of the corresponding monogenic disorders. Clinical implications of having CRGV or VUS should be explored. This article is protected by copyright. All rights reserved.

Background: There is inadequate information on the validation of diabetic microvascular complications in the Korean National Health Insurance Service data set. We aimed to validate the diagnostic algorithms regarding the nephropathy, neuropathy, and retinopathy of diabetes.Methods: From various secondary and tertiary medical centers, we selected 6,493 patients aged ≥ 40 years who were diagnosed with diabetic microvascular complications more than once based on codes in the 10th version of the International Classification of Diseases (ICD-10). During 2019 and 2020, we randomly selected the diagnoses of 200 patients, 100 from each of two hospitals. The positive predictive value (PPV), negative predictive value, error rate, sensitivity, and specificity were determined for each diabetic microvascular complication according to the ICD-10 codes, laboratory findings, diagnostic studies, and treatment procedure codes.Results: Among the 200 patients who visited the hospital more than once and had the diagnostic codes of diabetic microvascular complications, 142, 110, and 154 patients were confirmed to have the gold standard of diabetic nephropathy (PPV, 71.0%), diabetic neuropathy (PPV, 55.0%), and diabetic retinopathy (PPV, 77.0%), respectively. The PPV and specificity of diabetic nephropathy (PPV, 71.0–81.4%; specificity, 10.3–53.4%), diabetic neuropathy (PPV, 55.0–81.3%; specificity, 66.7–76.7%) and diabetic retinopathy (PPV, 77.0–96.6%; specificity, 2.2–89.1%) increased after combining them with the laboratory findings, diagnostic studies, and treatment procedures codes. These change trends were observed similarly for both hospitals.Conclusions: Defining diabetic microvascular complications using ICD-10 codes and their related examination codes may be a feasible method for studying diabetic complications.

Introduction Although treatment of OSA in patients with ischemic stroke is important for secondary prevention of stroke and improving neurologic outcomes, patients with stroke often are not adherent to nasal CPAP. The aim of the study is to examine the adherence rate and explore the predictive factors for CPAP compliance in patients with a recent history of ischemic stroke. Methods We reviewed the medical records of patients with ischemic stroke who were diagnosed with OSA after the onset of stroke and those who were recommended to use nasal CPAP at a single university Hospital from March 2020 to November 2022. Demographic information, neurologic functional status, and polysomnographic data were reviewed. For patients who agreed to use CPAP, CPAP compliance data were analyzed using cloud data run by various CPAP companies. Results 76 patients with cerebral infarction or transient ischemic attack were diagnosed with OSA and were recommended to use nasal CPAP (mean age, 60.8±12.6, male 60). Night PSG was performed after the onset of the stroke as the evaluation process for risk factors for stroke based on clinical symptoms such as snoring or apnea. The acceptance rate for nasal CPAP was 88.1% (67/76) at the first visit after the PSG. The adherence rate was 55.2% (37/67). No difference between the adherent and non-adherent groups was found in polysomnographic variables, including AHI, RDI, and subjective sleep scales such as PSQI, ISI, and ESS. No difference in the neurologic functional deficit was found between the groups. The adherent group was younger but not statistically significant (58.4±13.10 vs. 63.6±11.65, p=0.10). Female patients with ischemic stroke were more intolerant to CPAP (24.1% vs. 11.7%). Conclusion The patients in our study performed a PSG due to the risk evaluation of stroke rather than pursuing treatment for sleep apnea symptoms. Half of the patients were not adherent to CPAP, although they agreed to try CPAP. The proper screening of sleep apnea and education on sleep apnea and its impact on the neurologic outcome would be mandated to increase CPAP adherence in patients with ischemic stroke. Support (if any) Basic Science Research Program through NRF funded by the Ministry of Education(2021R1I1A1A01059791)

ObjectiveTo improve epidemiologic knowledge of neurologic deterioration (ND) in patients with acute ischemic stroke (AIS).MethodsIn this prospective observational study, we captured ND prospectively in 29,446 patients with AIS admitted to 15 hospitals in Korea within 7 days of stroke onset. ND was defined as an increase in NIH Stroke Scale (NIHSS) score ≥2 (total), or ≥1 (motor or consciousness), or any new neurologic symptoms. Change in incidence rate after stroke onset, causes, factors associated with ND, modified Rankin Scale (mRS) score at 3 months and 1 year, and a composite of stroke, myocardial infarction, and all-cause death at 1 year were assessed.ResultsND occurred in 4,299 (14.6%) patients. The highest rate, 6.95 per 1,000 person-hours incidence, was within the first 6 hours, which decreased to 2.09 within 24–48 hours, and 0.66 within 72–96 hours after stroke onset. Old age, female sex, diabetes, early arrival, large artery atherosclerosis as a stroke subtype, high NIHSS scores, glucose level, systolic blood pressure, leukocytosis at admission, recanalization therapy, TIA without a relevant lesion, and steno-occlusion of relevant arteries were associated with ND. The causes were stroke progression (71.8%) followed by recurrence (8.5%). Adjusted relative risks (95% CI) for poor outcome (mRS 3–6) at 3 months and 1 year were 1.75 (1.70–1.80) and 1.70 (1.65–1.75), respectively. The adjusted hazard ratio (95% CI) for the composite event was 1.59 (1.45–1.74).ConclusionsND should be taken into consideration as a factor that may influence the outcome in acute ischemic stroke.

ObjectiveStroke is a devastating and costly disease; however, there is a paucity of information on long-term costs and on how they differ according to 3-month modified Rankin scale (mRS) score, which is a primary outcome variable in acute stroke intervention trials.MethodsWe analyzed a prospective multicenter stroke registry (Clinical Research Collaboration for Stroke in Korea) database through linkage with claims data from the National Health Insurance Service with follow-up to December 2016. Healthcare expenditures were converted into daily cost individually, and annual and cumulative costs up to 5 years were estimated and compared according to the 3-month mRS score.ResultsBetween January 2011 and November 2013, 11,136 patients were enrolled in the study. The mean age was 68 years, and 58% were men. The median follow-up period was 3.9 years (range 0–5 years). Mean cumulative cost over 5 years was $117,576 (US dollars [USD]); the cost in the first year after stroke was the highest ($38,152 USD), which increased markedly from the cost a year before stroke ($8,718 USD). The mean 5-year cumulative costs differed significantly according to the 3-month mRS score (p < 0.001); the costs for a 3-month mRS score of 0 or 5 were $53,578 and $257,486 USD, respectively. Three-month mRS score was an independent determinant of long-term costs after stroke.ConclusionsWe show that 3-month mRS score plays an important role in the prediction of long-term costs after stroke. Such estimates relating to 3-month mRS categories may be valuable when undertaking health economic evaluations related to stroke care.

Background: The CHADS2, CHA2DS2-VASc, ATRIA, and Essen scores have been developed for predicting vascular outcomes in stroke patients. We investigated the association between these stroke risk scores and unsuccessful recanalization after endovascular thrombectomy (EVT). Methods: From the nationwide multicenter registry (Selection Criteria in Endovascular Thrombectomy and Thrombolytic therapy (SECRET)) (Clinicaltrials.gov NCT02964052), we consecutively included 501 patients who underwent EVT. We identified pre-admission stroke risk scores in each included patient. Results: Among 501 patients who underwent EVT, 410 (81.8%) patients achieved successful recanalization (mTICI ≥ 2b). Adjusting for body mass index and p < 0.1 in univariable analysis revealed the association between all stroke risk scores and unsuccessful recanalization (CHADS2 score: odds ratio (OR) 1.551, 95% confidence interval (CI) 1.198–2.009, p = 0.001; CHA2DS2VASc score: OR 1.269, 95% CI 1.080–1.492, p = 0.004; ATRIA score: OR 1.089, 95% CI 1.011–1.174, p = 0.024; and Essen score: OR 1.469, 95% CI 1.167–1.849, p = 0.001). The CHADS2 score had the highest AUC value and differed significantly only from the Essen score (AUC of CHADS2 score; 0.618, 95% CI 0.554–0.681). Conclusion: All stroke risk scores were associated with unsuccessful recanalization after EVT. Our study suggests that these stroke risk scores could be used to predict recanalization in stroke patients undergoing EVT.

BackgroundAlthough many electrocardiography wearable devices have been released recently for the detection of atrial fibrillation (AF), there are few studies reporting prospective data for wearable devices compared to the strategy of the existing guidelines in the detection of atrial fibrillation (AF) after cryptogenic stroke. A tiny single-patch monitor is more convenient than a conventional Holter monitor recording device and, therefore, longer duration of monitoring may be acceptable.Methods and DesignThe CANDLE-AF study is a multicenter, prospective, randomized controlled trial. Patients with transient ischemic attack or ischemic stroke without any history of AF will be enrolled. The superiority of the 72-h single-patch monitor to standard strategy and non-inferiority of the 72-h single-patch monitor to an event-recorder-type device will be investigated. Single-patch monitor arm will repeat monitoring at 1, 3, 6, and 12 months, event-recorder-type arm will repeat monitoring twice daily for 12 months. The enrollment goal is a total of 600 patients, and the primary outcome is the detection of AF which continues at least 30 s during study period. The secondary outcome is the rate of changes from antiplatelet to anticoagulant and major adverse cardiac and cerebrovascular events within 1 year.ConclusionsThe results of CANDLE-AF will clarify the role of a single-lead patch ECG for the early detection of AF in patients with acute ischemic stroke. In addition, the secondary outcome will be analyzed to determine whether more sensitive AF detection can affect the prognosis and if further device development is meaningful. (cris.nih.go.kr KCT0005592).

Background: The CHADS2, CHA2DS2-VASc, ATRIA, and Essen scores have been developed for predicting vascular outcomes in stroke patients. We investigated the association between these stroke risk scores and unsuccessful recanalization after endovascular thrombectomy (EVT). Methods: From the nationwide multicenter registry (Selection Criteria in Endovascular Thrombectomy and Thrombolytic therapy (SECRET)) (Clinicaltrials.gov NCT02964052), we consecutively included 501 patients who underwent EVT. We identified pre-admission stroke risk scores in each included patient. Results: Among 501 patients who underwent EVT, 410 (81.8%) patients achieved successful recanalization (mTICI ≥ 2b). Adjusting for body mass index and p < 0.1 in univariable analysis revealed the association between all stroke risk scores and unsuccessful recanalization (CHADS2 score: odds ratio (OR) 1.551, 95% confidence interval (CI) 1.198–2.009, p = 0.001; CHA2DS2VASc score: OR 1.269, 95% CI 1.080–1.492, p = 0.004; ATRIA score: OR 1.089, 95% CI 1.011–1.174, p = 0.024; and Essen score: OR 1.469, 95% CI 1.167–1.849, p = 0.001). The CHADS2 score had the highest AUC value and differed significantly only from the Essen score (AUC of CHADS2 score; 0.618, 95% CI 0.554–0.681). Conclusion: All stroke risk scores were associated with unsuccessful recanalization after EVT. Our study suggests that these stroke risk scores could be used to predict recanalization in stroke patients undergoing EVT.

Periodontitis is a common chronic inflammatory disease and one of oral complications in diabetes. Diabetes-related microvascular complications and periodontitis are also closely related to systemic inflammation. We hypothesized that periodontitis and oral hygiene markers might increase the risk of microvascular complications in diabetes mellitus.We enrolled 11,353 diabetes participants without prior microvascular complications who received complete oral health checkups in the National Health Insurance Service-National Health Screening Cohort in 2003-2004. The primary outcome was the first development of diabetes-related microvascular complications, including nephropathy, neuropathy, and retinopathy.The age of all participants was 55.27 ± 9.46 years, and 7833 (68.99%) participants were male. Periodontitis was noted in 8.37%. During the 7.03 ± 4.30 year of the mean follow-up period, 7227 patients experienced diabetes-related microvascular complications (2645 with nephropathy, 2513 with neuropathy, 2069 with retinopathy). Multivariable Cox regression analyses revealed that periodontitis was an independent risk factor for diabetes-related microvascular complications (adjusted hazard ratio (HR):1.13; 95% confidence interval (CI):1.04-1.23; p = 0.004). In the secondary analysis for individual microvascular complications, periodontitis was an independent risk factor for retinopathy (adjusted HR: 1.21; 95% CI: 1.04-1.40; p = 0.013).The presence of periodontitis was associated with an increased risk of microvascular complications in diabetes patients.

Background: CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores are used to estimate thromboembolism risk. We aimed to investigate the association between unfavorable outcomes and stroke risk scores in patients who received endovascular thrombectomy (EVT). Methods: This study was performed using data from a nationwide, multicenter registry to explore the selection criteria for patients who would benefit from reperfusion therapies. We calculated pre-admission CHADS2, CHA2DS2-VASc, ATRIA, and Essen scores for each patient who received EVT and compared the relationship between these scores and 3-month modified Rankin Scale (mRS) records. Results: Among the 404 patients who received EVT, 213 (52.7%) patients had unfavorable outcomes (mRS 3–6). All scores were significantly higher in patients with unfavorable outcomes than in those with favorable outcomes. Multivariable logistic regression analysis indicated that CHADS2 and the ATRIA score were positively correlated with unfavorable outcomes after adjusting for body mass index and variables with p < 0.1 in the univariable analysis (CHADS2 score: odds ratio [OR], 1.484; 95% confidence interval [CI], 1.290–1.950; p = 0.005, ATRIA score, OR, 1.128; 95% CI, 1.041–1.223; p = 0.004). Conclusions: The CHADS2 and ATRIA scores were positively correlated with unfavorable outcomes and could be used to predict unfavorable outcomes in patients who receive EVT.

ObjectiveIntracranial atherosclerosis is a major cause of ischaemic stroke worldwide. A number of studies have shown the effects of statin treatment on coronary and carotid artery plaques, but there is little evidence on the effects of statin treatment on intracranial atherosclerotic plaques.MethodsThe Intensive Statin Treatment in Acute Ischaemic Stroke Patients with Intracranial Atherosclerosis - High-Resolution Magnetic Resonance Imaging (STAMINA-MRI) Trial is a single-arm, prospective, observational study monitoring imaging and clinical outcomes of high-dose statin treatment among statin-naive patients with acute ischaemic stroke caused by symptomatic intracranial atherosclerosis. The primary outcome was the change in vascular remodelling and plaque characteristics before and after 6 months (median: 179 days, IQR 163–189 days) of statin treatment measured by high-resolution MRI (HR-MRI).ResultsA total of 77 patients (mean age: 62.6±13.7 years, 61.0% women) were included in this study. Low-density lipoprotein cholesterol (LDL-C) levels (mg/dL) at initial and follow-up assessments were 125.81±35.69 and 60.95±19.28, respectively. Overall, statin treatment significantly decreased enhancement of plaque volume (mm3, 32.07±39.15 vs 17.06±34.53, p=0.013), the wall area index (7.50±4.28 vs 5.86±4.05, p=0.016) and stenosis degree (%, 76.47±20.23 vs 64.05±21.29, pConclusionsHigh-dose statin treatment effectively stabilised symptomatic intracranial atherosclerotic plaques as documented by HR-MRI. Further study is needed to determine laboratory and genetic factors associated with poor response to statins and alternative therapeutic options, such as proprotein convertase subtilisin-kexin type 9 inhibitors, for these patients.Trial registration numberClinicalTrials.gov NCT02458755.

Despite the great socioeconomic burden of stroke, there have been few reports of stroke statistics in Korea. In this scenario, the Epidemiologic Research Council of the Korean Stroke Society launched the “Stroke Statistics in Korea” project, aimed at writing a contemporary, comprehensive, and representative report on stroke epidemiology in Korea. This report contains general statistics of stroke, prevalence of behavioral and vascular risk factors, stroke characteristics, pre-hospital system of care, hospital management, quality of stroke care, and outcomes. In this report, we analyzed the most up-to-date and nationally representative databases, rather than performing a systematic review of existing evidence. In summary, one in 40 adults are patients with stroke and 232 subjects per 100,000 experience a stroke event every year. Among the 100 patients with stroke in 2014, 76 had ischemic stroke, 15 had intracerebral hemorrhage, and nine had subarachnoid hemorrhage. Stroke mortality is gradually declining, but it remains as high as 30 deaths per 100,000 individuals, with regional disparities. As for stroke risk factors, the prevalence of smoking is decreasing in men but not in women, and the prevalence of alcohol drinking is increasing in women but not in men. Population-attributable risk factors vary with age. Smoking plays a role in young-aged individuals, hypertension and diabetes in middle-aged individuals, and atrial fibrillation in the elderly. About four out of 10 hospitalized patients with stroke are visiting an emergency room within 3 hours of symptom onset, and only half use an ambulance. Regarding acute management, the proportion of patients with ischemic stroke receiving intravenous thrombolysis and endovascular treatment was 10.7% and 3.6%, respectively. Decompressive surgery was performed in 1.4% of patients with ischemic stroke and in 28.1% of those with intracerebral hemorrhage. The cumulative incidence of bleeding and fracture at 1 year after stroke was 8.9% and 4.7%, respectively. The direct costs of stroke were about ₩1.68 trillion (KRW), of which ₩1.11 trillion were for ischemic stroke and ₩540 billion for hemorrhagic stroke. The great burden of stroke in Korea can be reduced through more concentrated efforts to control major attributable risk factors for age and sex, reorganize emergency medical service systems to give patients with stroke more opportunities for reperfusion therapy, disseminate stroke unit care, and reduce regional disparities. We hope that this report can contribute to achieving these tasks.

BackgroundWe investigated the microRNA expression pattern from thrombus retrieved by mechanical thrombectomy in acute stroke patients to understand the stroke mechanism.MethodsThis study included acute ischemic stroke patients who had undergone intra-arterial thrombectomy at Chung-Ang University Hospital in Seoul, Korea between February 2016 and March 2019. The thrombus was retrieved and stored at −70℃ after obtaining informed consent. MicroRNA microarray analysis was performed for the patients with identified stroke mechanisms including (1) large artery atherosclerosis, (2) cardioembolism with atrial fibrillation, and (3) cardioembolism with valvular heart disease. The microRNAs derived from microarray analysis were validated by quantitative real-time polymerase chain reaction (qRT-PCR) from different patient populations. The correlation analysis was performed between microRNA levels and laboratory data to understand the functional relevance of the altered microRNA.ResultsIn total, 55 thrombi were obtained from 74 patients, and the microRNAs were analyzed in 45 samples. Microarray analysis of 2578 microRNAs revealed that 50 microRNAs were significantly altered among the three groups. Validation using qRT-PCR showed that miR-378f and miR-450b-5p were significantly elevated among the cardioembolic thrombi; both microRNAs were inversely correlated with the ejection fraction from echocardiography. Thrombi from patients with early neurological deterioration exhibited higher levels of miR-93-5p and lower levels of miR-629-5p than those from neurologically stable patients.ConclusionsThe microRNA expression pattern can provide information regarding the mechanism of stroke by reflecting the underlying pathological status of the organ from which the thrombus was derived.

Background: The significance of silent brain infarction (SBI) for stroke recurrence in acute ischemic stroke (AIS) patients with atrial fibrillation (AF) has yet to be elucidated. This study aims to evaluate SBI as an independent predictor and which characteristics of SBI are associated with stroke recurrence in AIS patients with AF. Methods: A multicenter prospective cohort recruited AIS patients with non-valvular AF from 14 centers from Oct 2017 to Dec 2018, and followed for ischemic stroke recurrence, all types of stroke and TIA, and all-cause mortality. Three patient groups; stroke patients with prior stroke history (PS), first-ever stroke with SBI [F-SBI(+)] and first-ever stroke without SBI [F-SBI(-)] were compared with Cox frailty model according to predetermined covariates. SBI subtypes; embolic-appearing pattern (EAP) and non-EAP, and SBI characteristics; size, numbers, and vascular territory involvements were assessed. Results: A total of 978 AF-AIS patients [27.5% PS, 29.1% F-SBI(+), 43.4% F-SBI(-)] were followed for 365 [348-374] days (median). Incidence of ischemic stroke recurrence in F-SBI(+) was higher than F-SBI(-), however, there was no significant difference compared to PS (p=0.860). Adjusted hazards for ischemic stroke recurrence and all kinds of stroke and TIA in F-SBI(+) were shown to be elevated [HR 3.87 (95% CI 1.53-9.16) and 2.60 (1.21-5.56)], and similar to PS [4.20 (1.73-10.24) and 2.90 (1.36-6.18)] when compared to F-SBI(-), respectively. Despite irrelevance in non-EAP SBI, a 4-fold increase of hazards in EAP SBI was observed [4.07 (1.63-10.13)]. Other SBI characteristics were not associated with outcomes. SBI and SBI features did not increase all-cause mortality. Conclusions: SBI and specifically, EAP SBI elevated stroke recurrence in AF-AIS patients as much prior stroke has increased the risk. Considering SBI to predict recurrence is suggested likewise prior stroke history is scored in AF thromboembolic risk estimation tools.

Background and Purpose Osteoprotegerin (OPG) is a component of the tumor necrosis factor receptor superfamily. Several studies have shown a relationship between OPG and cardiovascular diseases. We hypothesized that there is a relationship between plasma OPG levels and cerebral small vessel disease (SVD). Methods Patients diagnosed with their first cerebral ischemic infarction between April 2014 and March 2017 were enrolled. All the enrolled patients were evaluated through the hospital stroke protocol, including routine blood tests, brain imaging, and measuring the plasma OPG levels. The presence and burden of cerebral SVD [cerebral microbleeds (CMBs), asymptomatic lacunar infarction (ALI), high-grade perivascular space (HPVS), high-grade white matter hyperintensity (HWMH)], and total SVD score were assessed through brain magnetic resonance imaging. Results Of the 270 patients included in our study, 158 (58.5%) were men. The mean age of the patients was 63.8 ± 11.6 years. In multivariable analysis, plasma OPG levels were positively associated with the presence and burden of each cerebral SVD. The odds ratios (OR) of CMBs, ALI, HPVS, and HWMH for the association of OPG per standard deviation (SD) increase were 1.58 [95% confidence interval (CI), 1.09–2.27], 1.40 (95% CI, 1.04-1.88), 1.88 (95% CI, 1.27–2.78), and 1.47 (95% CI, 1.04–2.08), respectively. Plasma OPG levels were positively correlated with total SVD score (beta = 0.211, standard error = 0.061, p-value = 0.009, R2 = 0.275). Conclusions Plasma OPG levels correlate with the presence and burden of cerebral SVD in patients with acute ischemic stroke.

Background The long‐term incidence of acute myocardial infarction (AMI) in patients with acute ischemic stroke (AIS) has not been well defined in large cohort studies of various race‐ethnic groups. Methods and Results A prospective cohort of patients with AIS who were registered in a multicenter nationwide stroke registry (CRCS‐K [Clinical Research Collaboration for Stroke in Korea] registry) was followed up for the occurrence of AMI through a linkage with the National Health Insurance Service claims database. The 5‐year cumulative incidence and annual risk were estimated according to predefined demographic subgroups, stroke subtypes, a history of coronary heart disease (CHD), and known risk factors of CHD. A total of 11 720 patients with AIS were studied. The 5‐year cumulative incidence of AMI was 2.0%. The annual risk was highest in the first year after the index event (1.1%), followed by a much lower annual risk in the second to fifth years (between 0.16% and 0.27%). Among subgroups, annual risk in the first year was highest in those with a history of CHD (4.1%) compared with those without a history of CHD (0.8%). The small‐vessel occlusion subtype had a much lower incidence (0.8%) compared with large‐vessel occlusion (2.2%) or cardioembolism (2.4%) subtypes. In the multivariable analysis, history of CHD (hazard ratio, 2.84; 95% CI, 2.01–3.93) was the strongest independent predictor of AMI after AIS. Conclusions The incidence of AMI after AIS in South Korea was relatively low and unexpectedly highest during the first year after stroke. CHD was the most substantial risk factor for AMI after stroke and conferred an approximate 5‐fold greater risk.

The aim of this study is to investigate the influence of white matter hyperintensity (WMH) on stroke severity and prognosis in patients with symptomatic carotid artery stenosis. Patients with symptomatic carotid artery stenosis were retrieved from the Samsung Medical Center stroke registry from January 2011 to December 2016. Stroke severity was categorized into three levels according to National Institutes of Health Stroke Scale (NIHSS): transient ischemic attack (TIA) or transient symptoms with infarction (TSI), mild stroke, and moderate to severe stroke. WMH volume was measured with medical image processing and visualization. The clinical outcome was assessed using the modified Rankin scale on the 90th day from which the latest onset of the neurological symptom. Logistic regression was used to predict stroke severity, and ordinal regression was used to compare the clinical outcome. Among 158 patients, the numbers of patients with TIA or TSI, mild stroke, and moderate to severe stroke were 48 (30.4%), 59 (37.3%), and 51 (32.3%), respectively. The larger WMH volume was associated with moderate to severe strokes (TIA/TSI vs. moderate to severe strokes, odds ratio (OR) 2.318, 95% confidence interval (CI) 1.194–4.502, p = 0.007; mild vs. moderate to severe strokes, OR 1.972, 95% CI 1.118–3.479, p = 0.013). Patients with larger volume of WMH showed poorer clinical outcome (cutoff value: 9.71 cm3, OR 2.099, 95% CI 1.030–4.311, p = 0.042). Our study showed that larger WMH volume is associated with more severe stroke and poorer prognosis in patients with symptomatic carotid artery stenosis.

Background and aims: The pathophysiology of hippocampal enlarged perivascular spaces (H-EPVS) and its relationship to cognitive impairment is largely unknown. This study aimed to investigate the relationship between H-EPVS and cognition in non-dementic elderly population.Methods: A total of 109 subjects were prospectively enrolled. The eligibilities for inclusion were age from 55 to 85 years and Mini-Mental Status Examination score of ≥26. The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Montreal Cognitive Assessment, transcranial Doppler (TCD), and brain magnetic resonance imaging results were evaluated. H-EPVS was categorized in a three-degree scale: degree 0 (no), degree 1 (1,2), and degree 2 (>2). The associations between H-EPVS and TCD parameters/cognitive test profiles were analyzed.Results: The mean age was 65.2 years, and 52.3% subjects were men. H-EPVS was found to be associated with age (degree 2 vs. degree 1 vs. degree 0, 69.20 ± 6.93 vs. 65.70 ± 5.75 vs. 63.80 ± 5.43; p = 0.030) and ADAS-Cog memory score (degree 2 vs. degree 1 vs. degree 0, 14.88 ± 4.27 vs. 12.49 ± 4.56 vs. 11.4 ± 4.23; p = 0.037). However, the pulsatility index was not related to the degree of H-EPVS. Multivariate analysis revealed medial temporal atrophy (MTA) scale score was independently associated with ADAS-Cog memory score (MTA scale sum ≥4, p = 0.011) but not with the degree of H-EPVS. MTA scale score showed correlation with H-EPVS (r = 0.273, p = 0.004).Conclusions: Aging was associated with the development of H-EPVS in non-dementic elderly population. Memory function was found to be associated with MTA but not with the degree of H-EPVS.

Supplemental Digital Content is available in the text., Background and Purpose: Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events. Methods: In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–30) or placebo added to aspirin (300–325 mg on day 1 followed by 75–100 mg daily for days 2–30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days. Results: Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56–0.96], P=0.023) resulting in a number needed to treat of 34 (95% CI, 19–171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74–1.08]; P=0.23, Pinteraction=0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively (P=NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04–16.9], P=0.001). Conclusions: In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19–171). Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03354429.

Background Off‐hour presentation can affect treatment delay and clinical outcomes in endovascular therapy ( EVT ) for acute ischemic stroke. We aimed to examine the treatment delays and clinical outcomes of EVT between on‐ and off‐hour admission and to evaluate the effect of hospital procedure volume and the number of neurointerventionalists on off‐hour EVT . Methods and Results From a multicenter registry, we identified patients who were treated with EVT within 12 hours of symptom. Annual hospital procedure volume was divided as low (60). The effect of the number of neurointerventionalists and annual hospital procedure volume on clinical outcome was estimated by the generalized estimation equation. Of the 31 133 stroke patients, 1564 patients met the eligibility criteria (mean age: 69±12 years; median baseline National Institutes of Health stroke scale score, 15 [interquartile range, 10–19]). Of 1564 patients, 893 (57.1%) arrived during off‐hour. The off‐hour patients had greater median door‐to‐puncture time (110 versus 95 minutes; P P =0.90). The presence of three neurointerventionalists was significantly associated with favorable outcomes at 3 months during on‐ and off‐hour (2.07 [1.53–2.81]; P Conclusions The number of neurointerventionalists was more crucial to effective around‐the‐clock EVT for acute stroke patients than hospital procedural volume.

Background: Risk stratification of asymptomatic carotid artery stenosis (ACAS) is still an issue for carotid revascularization. We sought to identify factors associated with symptomatic carotid artery stenosis (SCAS) using multimodal imaging techniques.Methods: We retrospectively collected data on patients who underwent carotid artery revascularization. Results from duplex sonography, computerized tomography angiography, brain magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), perfusion-weighted imaging, and demographic profiles were compared between ACAS and SCAS patients. Differences in baseline characteristics between the two groups were balanced by the propensity matching score method. Multivariable regression analysis was performed to identify factors associated with symptomaticity of carotid artery stenosis. We compared the strength of associations between significant imaging factors and symptomatic carotid stenosis using C statistics.Results: A total of 259 patients (asymptomatic 57.1%, symptomatic 42.9%) with carotid stenosis were included. After 1:1 propensity score matching, the multivariable regression analysis revealed that the absence of plaque calcification [Odds ratio 0.41, 95% confidence interval (CI) 0.182–0.870, p = 0.023], deep white matter hyperintensity (DWMH; Odds ratio 3.46, 95% CI 1.842–6.682, p < 0.001), susceptibility vessel sign seen on gradient-echo MRI (Odds ratio 2.35, 95% CI 1.113–5.107, p = 0.027), and increased cerebral blood volume (CBV) seen on perfusion-weighted MRI (CBV; Odds ratio 2.17, 95% CI 1.075–4.454, p = 0.032) were associated with SCAS. The combination of these variables had a fair accuracy to classify SCAS (Area under the curve 0.733, 95% CI 0.662–0.803).Conclusions: We identified several multimodal imaging markers independently associated with SCAS. These markers may provide information to identify ACAS patients with high risk of ischemic stroke. Future studies are needed to predict SCAS using our findings in other independent cohorts.

Background and Purpose: Stroke is one of the most devastating and costly health problems of today. However, there is lack of knowledge about how costly it is in a long-term perspective and how much the long-term cost differs according to 3-month functional outcome, a major primary outcome variable of acute stroke intervention trials. Methods: Acute ischemic stroke patients who were registered into the multi-center stroke registry (Clinical Research Collaboration for Stroke in Korea, CRCS-K) in South Korea between 2011 and 2013 were matched to the National Health Insurance Service claim database. All the healthcare expenditure was extracted from the claim database and converted into daily cost of each individual. Yearly expenditures and cumulative expenditure up to 5 yeas were obtained and expressed in US dollars and were compared according to 3-month functional outcome (modified Rankin disability scale, mRS).Results: A total of 11,136 acute ischemic stroke patients (mean age, 68 years; men 58%) were analyzed. The median follow-up period was 1,418 days. The mean cumulative healthcare expenditure over 5 years was $74,295 (SD, $91,049) and showed a dramatic increment during the first month followed by a constant increase without a considerable change. The mean 5-year cumulative expenditure differed significantly according to 3-month functional outcome; $32,261 in those with 3-month mRS 0 and $163,244 in those with 3-month mRS 5. After adjusting for the selected potential confounders, the yearly expenditures and the cumulative one at each time point differed significantly according to 3-month mRS scores. Figure given below is showing the median 5-year cumulative daily expenditure by 3-month mRS. Conclusions: This study shows that the impact of 3-month functional outcome on the long-term healthcare expenditure following acute ischemic stroke may be more than expected. The efforts for improving functional outcomes are urgent.

Background: Stroke unit care is recommended as a standard care for acute stroke. We sought to determine whether morbidity and mortality of patients who admitted for acute ischemic stroke have been improved after implementation of stroke unit care in a regional public hospital. Methods: Seoul Medical Center is a regional public hospital in Seoul, the capital of Korea. Stroke unit has been established at June, 2011. Information of all consecutive stroke patients admitted to our hospital including functional outcome has been collected prospectively from April, 2008 as a part of a nationwide multicenter stroke registry. We compared outcomes of pre and post commencement of stroke unit, obtained from April, 2008 to December, 2010 and from January 2012 to November 2017, respectively. Primary outcome was a good functional outcome defined as a modified Rankin scale score of 2 or less at 3 months. A secondary outcome was death at 3 months. Results: Of all acute ischemic stroke, 366 and 1540 patients were identified as pre and post commencement of stroke unit. There were no significant differences in mean age (69.5±13.1 years versus 69.2±12.2 years; p =.684), sex distribution (male, 59.8% versus 59.4%, p =.906) and mean National Institutes of Health Stroke Scale score at admission (5.7±5.4 versus 5.6±5.9, p =.759) between two epochs. Good functional outcome was increased from 46.4% to 53.6% ( p =.015) while mortality at 3 months dropped from 11.7 % to 5.4% ( p Conclusions: Our study shows the improvement of outcomes in patients with acute ischemic stroke after commencement of stroke unit care. Stroke unit care service needs to be expanded in other regional public hospitals in Korea.

Background and aims Elevated serum homocysteine level is known to be associated with increased risk of vascular event due to endothelial senescence. We investigated the association between serum homocysteine level and cerebral arteriosclerosis status including intracranial vascular calcification and atherosclerosis burden. Methods We identified 1193 consecutive patients (mean age = 68.6 ± 12.7, 537 female patients) who were admitted with acute cerebral infarction or transient ischemic attack from a single university medical center. The patients were categorized into three groups according to their serum homocysteine level. Cerebral artery calcification was assessed from the cavernous portion of both internal carotid arteries, and cerebral atherosclerosis burden was derived as the sum of stenosis degree of major intracranial arteries from brain computed tomography angiography. Results The mean homocysteine level was 14.1 ± 6.2 μmol/L, and intracranial cerebral artery calcification was present in 974 patients (81.6%), with 339 cases of advanced calcification (28.4%). The prevalence of cerebral artery calcification, advanced cerebral artery calcification and cerebral atherosclerosis burden showed increasing tendency throughout the homocysteine tertiles. Multivariable logistic regression analysis including age, sex, vascular risk factors, serum C-reactive protein, estimated glomerular filtration rate and homocysteine tertile disclosed that the highest serum homocysteine tertile was an independent predictor of advanced cerebral artery calcification (odds ratio = 1.45, confidence interval = 1.02–2.05) and advanced cerebral atherosclerosis (odds ratio = 1.42, confidence interval = 1.01–1.99) compared to the lowest group. Conclusions An elevated serum homocysteine level was independently associated with intracranial arterial calcification and atherosclerosis burden. Future studies are warranted to test whether lowering serum homocysteine can delay cerebral arteriosclerotic changes.

The objective of this study was to investigate the potential benefits of statin therapy initiation in acute stroke in patients with active cancer. This study was conducted in two parts. First, data from patients who are presented with stroke and active cancer were obtained from prospectively collected multicenter hospital-based stroke registries. Patients were classified into statin user and non-user groups; the statin group was further divided into low-potency and high-potency statin subgroups. The primary outcome was time to mortality. Second, we obtained data from the Korean National Health Information Service-National Sample Cohort (NHIS-NSC) database for external validation and analyzed the effect of statins on mortality, taking compliance into consideration. For the stroke registry cohort, statin use was independently associated with reduced mortality in a multivariable model [hazard ratio (HR) = 0.675, 95% confidence interval (CI) = 0.457-0.996]. There was no interaction between statin use and cancer characteristics, vascular risk factors, or laboratory findings. A dose-dependent relationship between statin use and survival was also demonstrated. Analysis of the NHIS-NSC database found a similar association between statin therapy and reduced mortality (adjusted HR = 0.64, 95% CI = 0.45-0.90) and this effect persisted even after controlling for the adherence of statin use (HR = 0.60, 95% CI = 0.41-0.89). Statin therapy could be associated with reduced mortality in patients with acute stroke and active cancer.

Background: Intracranial occlusive disease is a common cause of stroke worldwide, and is more prevalent in Asians. We hypothesized that non-traumatic intracranial artery dissection (ICAD) may be a common hidden cause of large intracranial occlusive disease in Asian patients with ischemic stroke, and that many patients with ICAD may be misclassified as having intracranial atherosclerotic stenosis (ICAS). Methods: We prospectively recruited patients with acute symptomatic infarcts due to intracranial occlusive disease between January 2011 and October 2016. High-resolution magnetic resonance imaging (HR-MRI) was performed when vascular studies yielded ambiguous results for the diagnosis of ICAS, ICAD, or other causes. Clinical, laboratory, and HR-MRI findings were compared between the ICAS and ICAD groups. Results: Among 937 patients who showed intracranial stenosis on time-of-flight magnetic resonance angiography, HR-MRI was performed in 558. According to HR-MRI features, 123 were classified as ICAD and 252 as ICAS. Male sex, older age, hypertension, and diabetes were more frequent in the HR-confirmed ICAS group. Anterior circulation location, and the presence of vascular calcification and tandem stenosis were also more common in the ICAS group. However, clinical and radiological characteristics did not differ between patients with typical luminal changes of ICAD (n=69) and those with ICAD documented by HR-MRI but no typical luminal changes (n=123). Conclusion: Almost two thirds of ICAD patients in an Asian population were misclassified as having ICAS by standard luminal imaging techniques. Considering the different therapeutic and prognostic approaches in ICAD and ICAS, HR-MRI may be a useful diagnostic tool in this population.

ObjectiveTo compare the outcomes between patients with nontraumatic intracranial arterial dissection (ICAD) and intracranial atherosclerotic stenosis (ICAS) using high-resolution MRI (HR-MRI).MethodsWe conducted a prospective study using HR-MRI in patients with acute symptomatic cerebrovascular disease due to intracranial occlusive disease and no dissection on luminal images. Patients were followed-up for 27.9 ± 19.3 months. We compared the functional outcome, recurrence, and changes in vascular status between patients with ICAD (dissection and no plaque on HR-MRI) and ICAS (atherosclerosis plaque on HR-MRI).ResultsWe included 312 patients (mean age, 59.0 ± 14.2 years; men, 58.3%), of whom 113 had ICAD and 199 had ICAS. The functional outcome (as measured by modified Rankin Scale score) on the 90th day after symptom onset was not different between the groups, after adjusted for other factors (p = 0.095). However, recurrent ischemic cerebrovascular disease on the relevant vascular territory was lower in the ICAD group (7 patients, 6.2%) than in the ICAS group (37 patients, 18.6%). ICAD was a significant independent determinant of disease recurrence (hazard ratio, 0.43; 95% confidence interval, 0.19–0.98). Improvement in vascular stenosis on follow-up vascular studies was more frequently observed in ICAD (50.7%) than in ICAS (11.6%). ICAD was an independent determinant of vascular improvement (odds ratio, 7.94; 95% confidence interval, 3.32–19.01).ConclusionConsidering the high prevalence of ICAD in the patients with presumed ICAS and the differential outcomes between ICAD and ICAS, HR-MRI may be a useful diagnostic tool in this population.

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: Neurogenic pulmonary edema is non-cardiogenic pulmonary edema due to sudden excessive activation of sympathetic system after central nervous system injury. We report an acute cerebral infarction patient who developed neurogenic pulmonary edema requiring intubation and mechanical ventilation care. Case Report: A 77-year-old Korean woman visited emergency room complaining of sudden onset right side weakness which started one hour ago. She had a history of atrial fibrillation with normal ejection fraction. Neurological examination revealed motor aphasia and right side weakness. Brain computerized tomography angiography showed left middle cerebral artery occlusion without frank ischemic change. Intravenous thrombolytic therapy was considered, but suspended because she suddenly complained of respiration difficulty. Conclusions: This case suggests that large hemispheric infarction can result in acute onset pulmonary edema which is severe enough to require intubation and to delay thrombolytic treatment.

Background and purpose: Moyamoya disease (MMD) is a unique cerebrovascular occlusive disease that is characterized by progressive stenosis and negative remodeling of the distal internal carotid artery (ICA). We hypothesized that caveolin-1, a protein that controls the regulation of endothelial vesicular trafficking and signal transduction, is associated with negative remodeling in MMD. Methods: We prospectively recruited 77 consecutive patients with MMD (49 bilateral and 28 unilateral MMD) diagnosed by conventional angiography. Seventeen patients with intracranial atherosclerotic stroke and no RNF213 mutation served as controls. Distal ICA outer diameters were examined with high-resolution MRI. We evaluated whether the degree of negative remodeling in MMD patients was associated with RNF213 polymorphism, caveolin-1 levels, or various clinical and vascular risk factors. Results: The RNF213 variant was observed in 49 (63.6%) patients with MMD. The serum caveolin-1 (ng/mL) level was lower in MMD patients than in controls (0.47±0.29 vs. 0.86±0.68, P =0.034). The mean ICA diameter was 2.48±0.98 mm (range 0.00-4.76) for the 126 affected distal ICAs in MMD patients and 3.84±0.42 mm for asymptomatic ICAs in controls. After adjusting for possible confounders, male sex (coefficient, 0.396; P =0.029), clinical presentation with ischemic stroke (coefficient, -0.733; P P Conclusion: Our findings suggest that caveolin-1 may play a major role in arterial negative remodeling in MMD patients. Future studies exploring caveolin-1 as a therapeutic target in MMD are warranted.