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Abstract This study aimed to investigate the association between non-traditional lipid profiles and the risk of 1-year vascular events in patients who were already using statins before stroke and had admission LDL-C

Background Perfusion imaging (PI) serves as a valuable tool for triaging patients with acute ischemic stroke for endovascular treatment (EVT). This study aims to investigate trends in PI use and its impacts on EVT rates and clinical outcomes, particularly focusing on variations across different time windows. Methods Data from a prospective, nationwide, acute stroke registry in South Korea were analyzed retrospectively. PI was regarded as treatment‐decision imaging when conducted either (1) prior to EVT, or (2) within 3 hours from hospital arrival in patients not receiving EVT. The study spanned 3 epochs: 2011–2014, 2015–2017, and 2018–2021. Based on the time from onset to arrival, patients were categorized into 2 time windows: early (0–6 hours) and late (6–24 hours). We evaluated EVT rates and clinical outcomes in patients with anterior large vessel occlusion. Results From 2011 to 2021 among 49 449 patients with acute ischemic stroke presenting within 24 hours of onset, PI use rates declined from 36.9% to 30.1%. In the early window, rates dropped from 48.4% to 32.4%, whereas in the late window, they increased from 23.5% to 27.8%. Factors such as older age, atrial fibrillation, anterior large vessel occlusion, and severe stroke were associated with higher rates in the late window. Conversely, younger age and male sex were associated with higher rates in the early window. For patients with anterior large vessel occlusion, PI use increased the likelihood of receiving EVT in the late window and minimized the risk of symptomatic intracranial hemorrhage in the early window. However, 3‐month functional outcomes and mortality were. unaffected. Conclusion The study revealed distinct trends in PI use across early and late time windows, indicating varying roles of PI in these time frames. However, the definitive value and necessity of PI in guiding EVT decision‐making remain unclear, underscoring the need for further research

Abstract Introduction Visual field defects (VFDs) represent a debilitating poststroke complication, characterized by unseen parts of the visual field. Visual perceptual learning (VPL), involving repetitive visual training in blind visual fields, may effectively restore visual field sensitivity in cortical blindness. This current multicenter, double‐blind, randomized, controlled clinical trial investigated the efficacy and safety of VPL‐based digital therapeutics (Nunap Vision [NV]) for treating poststroke VFDs. Methods Stroke outpatients with VFDs (>6 months after stroke onset) were randomized into NV (defective field training) or Nunap Vision‐Control (NV‐C, central field training) groups. Both interventions provided visual perceptual training, consisting of orientation, rotation, and depth discrimination, through a virtual reality head‐mounted display device 5 days a week for 12 weeks. The two groups received VFD assessments using Humphrey visual field (HVF) tests at baseline and 12‐week follow‐up. The final analysis included those completed the study (NV, n = 40; NV‐C, n = 35). Efficacy measures included improved visual area (sensitivity ≥6 dB) and changes in the HVF scores during the 12‐week period. Results With a high compliance rate, NV and NV‐C training improved the visual areas in the defective hemifield (>72 degrees2) and the whole field (>108 degrees2), which are clinically meaningful improvements despite no significant between‐group differences. According to within‐group analyses, mean total deviation scores in the defective hemifield improved after NV training (p = .03) but not after NV‐C training (p = .12). Conclusions The current trial suggests that VPL‐based digital therapeutics may induce clinically meaningful visual improvements in patients with poststroke VFDs. Yet, between‐group differences in therapeutic efficacy were not found as NV‐C training exhibited unexpected improvement comparable to NV training, possibly due to learning transfer effects.

Background Recent clinical trials established the benefit of dual antiplatelet therapy with aspirin and clopidogrel (DAPT‐AC) in early‐presenting patients with minor ischemic stroke. However, the impact of these trials over time on the use and outcomes of DAPT‐AC among the patients with nonminor or late‐presenting stroke who do not meet the eligibility criteria of these trials has not been delineated. Methods and Results In a multicenter stroke registry, this study examined yearly changes from April 2008 to August 2022 in DAPT‐AC use for stroke patients ineligible for CHANCE/POINT (Clopidogrel in High‐Risk Patients with Acute Nondisabling Cerebrovascular Events/Platelet‐Oriented Inhibition in New TIA and Minor Ischemic Stroke) clinical trials due to National Institutes of Health Stroke Scale >4 or late arrival beyond 24 hours of onset. A total of 32 118 patients (age, 68.1±13.1 years; male, 58.5%) with National Institutes of Health Stroke Scale of 4 (interquartile range, 1–7) were analyzed. In 2008, DAPT‐AC was used in 33.0%, other antiplatelets in 62.7%, and no antiplatelet in 4.3%. The frequency of DAPT‐AC was relatively unchanged through 2013, when the CHANCE trial was published, and then increased steadily, reaching 78% in 2022, while other antiplatelets decreased to 17.8% in 2022 (Ptrend

Introduction: This trial, conducted according to the request of the Korean Ministry of Food and Drug Safety, investigated the potential of oxiracetam in mitigating post-stroke cognitive decline, and whether physical activity could augment its efficacy. The mechanisms behind these effects were explored using functional neuroimaging. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, we enrolled patients reporting subjective cognitive decline more than three months post-stroke and at a high risk of dementia. Participants were randomly assigned to a 36-week regimen of either 800 mg oxiracetam or a placebo, administered twice daily, in conjunction with recommended physical activity. Physical activity levels were monitored using wrist actigraphy. Cognitive function was assessed using a mini-mental state examination (MMSE) and clinical dementia rating sum of boxes (CDR-SB) at baseline and 36 weeks. Other assessments included the 60-minute protocol of Vascular Cognitive Impairment Harmonization Standards, Euro QoL, patient's global assessment, and resting-state functional MRI-derived neural network attributes. Results: Of the 500 participants (mean age 68.9 years, male 76.1%, median interval between stroke and randomization 32 months), 457 were analyzed. Both groups have equally adhered to the exercise guidelines (moderate-to-vigorous physical activity per day; 23.7±26.1 vs. 24.1±28.7 minutes; p=0.75). No significant difference was observed in changes to MMSE and CDR-SB scores between the two groups (MMSE, 0.13±2.27 vs. 0.27±2.09, p=0.49; CDR-SB -0.14±0.70 vs. -0.08±0.80, p=0.38). Although increased baseline exercise time correlated with better MMSE scores, the correlation was weak (R= 0.11, p=0.02). Verbal memory, phonemic fluency, language, NPI-Q, and geriatric depression scale also improved significantly within each group. However, only the intervention group showed significant improvements in CDR-SB and EuroQoL scores. A predetermined multivariate analysis showed a significant change in the normalized clustering coefficient for the secondary efficacy endpoint (r=0.09, SE=0.04, p=0.03). Discussion: This study failed to confirm the efficacy of oxiracetam in preventing post-stroke cognitive decline. Nonetheless, adherence to the exercise guidelines appeared to help participants maintain their cognitive functions, despite being a chronic stage post-stroke and having a high dementia risk.

Background and Rationale: Currently, there is no medication to prevent post-stroke cognitive decline. Previous studies have suggested that cilostazol may prevent cognitive decline in stroke through mechanisms such as increasing cerebral blood flow and reducing amyloid beta accumulation. We aimed to demonstrate the effectiveness of cilostazol, compared to aspirin or clopidogrel, in preventing cognitive decline in elderly patients with ischemic stroke at high risk of dementia. Study Design: We have designed a multicenter registry-based randomized controlled trial (RRCT), with an open-label blinded endpoint (PROBE) approach. We will recruit patients enrolled in the CRCS-K stroke registry who are at least three months from the onset of ischemic stroke and who meet the following conditions that suggest a high risk of developing dementia: age ≥ 75 years, age between 65 and 74 years and one of the following conditions: [diabetes mellitus, confluent white matter hyperintensities (Fazekas grade 3), medial temporal atrophy (Scheltens visual grade≥ 3), multiple cerebral microbleeds (≥ 5), multiple lacunes (> 5), APOE e4 allele]. Participants will be randomly allocated to either cilostazol (200 mg daily) or a control group receiving aspirin (100–300 mg daily) or clopidogrel (75 mg daily). Cognitive assessments will be performed at baseline, end of follow-up (up to 60 months), and whenever cognitive decline is reported by participants or caregivers. The study will be carried out across 17 centers in South Korea, with a projected enrollment of 2,362 patients. Study outcomes: Our primary outcome measure is the time from baseline to prespecified cognitive decline, defined as a decrease of 3 or more points on the MMSE and an increase of 1.5 or more points on the CDR-SOB. Secondary endpoints encompass changes in MMSE, CDR-SOB, and MoCA scores from baseline to final assessment, incident dementia, and a composite of recurrent stroke, acute myocardial infarction, and all-cause mortality. As a primary safety assessment, we will analyze the occurrence of major bleeding events. Discussion: We anticipate that the RRCT approach will enable efficient screening of a large cohort of elderly stroke patients at high risk of dementia while ensuring prolonged follow-up at a reasonable cost.

Background and Purpose Moderate-intensity statin plus ezetimibe versus high-intensity statin alone may provide a greater low-density lipoprotein cholesterol (LDL-C) reduction in patients with recent ischemic stroke. Methods This randomized, open-label, controlled trial assigned patients with recent ischemic stroke

Background It is unclear whether statin treatment could reduce the risk of early vascular events when baseline low‐density lipoprotein cholesterol (LDL‐C) levels are already low, at

Abstract Positron emission tomography with 18F-sodium fluoride (NaF) radioligand has been actively investigated in atherosclerosis research because it is known to detect microcalcification activity within atheroma. We studied whether NaF shows any uptake in the brain tissue of patients with acute ischemic stroke. This is a post-hoc analysis of previously reported cerebral atherosclerosis research with positron emission tomography which applied the two radioligands, 18F-fluorodeoxyglucose and NaF for the detection of culprit atheroma among 20 acute cerebral infarction patients (mean age = 75.1 ± 9.0 years; 10 women). In this study, we measured the maximum and mean standardized uptake value (SUVmax and SUVmean) of NaF uptake level in the cerebral infarct region between lesions with and without diffusion weighted image (DWI) positivity, indicating acute ischemic cell death. Correlation analysis was performed between NaF uptake levels and imaging and clinical variables, including neurological severity. The NaF uptake levels were significantly higher in DWI positive lesions than in negative lesions (SUVmax: 2.0 [0.60–4.2] versus 0.20 [0.10–0.40], p = 0.021 by Mann–Whitney U test). The intensity of NaF uptake (SUVmax) was significantly correlated with the initial neurological severity (Spearman's ρ = 0.579, p= 0.007) and white blood cell count (Spearman's ρ = 0.626, p p 0.003). During ischemic stroke NaF was concentrated in brain tissue undergoing acute cell death and its uptake intensity was correlated with neurological severity, suggesting that NaF could reflect acute ischemic cell death after stroke.

Abstract Background Higher pulsatility of the middle cerebral artery (MCA) is known to be associated with stroke progression. We investigated whether pulsatility index (PI) of the basilar artery (BA) can predict neurological deterioration (ND) after acute cerebral infarction. Methods A total of 708 consecutive patients with acute ischemic stroke who had undergone transcranial Doppler (TCD) ultrasonography were included. ND was defined as an increase in the National Institutes of Health Stroke Scale scores by two or more points after admission. The patients were categorized into quartiles according to BA PI. Multivariable logistic regression analysis was performed to examine whether BA PI is independently associated with ND. Results BA PI was well correlated with the right (n = 474, r2 = 0.573, P

Abstract We aimed to develop a novel prediction model for early neurological deterioration (END) based on an interpretable machine learning (ML) algorithm for atrial fibrillation (AF)-related stroke and to evaluate the prediction accuracy and feature importance of ML models. Data from multicenter prospective stroke registries in South Korea were collected. After stepwise data preprocessing, we utilized logistic regression, support vector machine, extreme gradient boosting, light gradient boosting machine (LightGBM), and multilayer perceptron models. We used the Shapley additive explanation (SHAP) method to evaluate feature importance. Of the 3,213 stroke patients, the 2,363 who had arrived at the hospital within 24 h of symptom onset and had available information regarding END were included. Of these, 318 (13.5%) had END. The LightGBM model showed the highest area under the receiver operating characteristic curve (0.772; 95% confidence interval, 0.715–0.829). The feature importance analysis revealed that fasting glucose level and the National Institute of Health Stroke Scale score were the most influential factors. Among ML algorithms, the LightGBM model was particularly useful for predicting END, as it revealed new and diverse predictors. Additionally, the effects of the features on the predictive power of the model were individualized using the SHAP method.

Abstract Background The Clock Drawing Test (CDT) and Rey–Osterrieth Complex Figure Test (RCFT) are widely used as a part of neuropsychological test batteries to assess cognitive function. Our objective was to confirm the prediction accuracies of the RCFT-copy and CDT for cognitive impairment (CI) using convolutional neural network algorithms as a screening tool. Methods The CDT and RCFT-copy data were obtained from patients aged 60–80 years who had more than 6 years of education. In total, 747 CDT and 980 RCFT-copy figures were utilized. Convolutional neural network algorithms using TensorFlow (ver. 2.3.0) on the Colab cloud platform ( www.colab.research.google.com ) were used for preprocessing and modeling. We measured the prediction accuracy of each drawing test 10 times using this dataset with the following classes: normal cognition (NC) vs. mildly impaired cognition (MI), NC vs. severely impaired cognition (SI), and NC vs. CI (MI + SI). Results The accuracy of the CDT was better for differentiating MI (CDT, 78.04 ± 2.75; RCFT-copy, not being trained) and SI from NC (CDT, 91.45 ± 0.83; RCFT-copy, 90.27 ± 1.52); however, the RCFT-copy was better at predicting CI (CDT, 77.37 ± 1.77; RCFT, 83.52 ± 1.41). The accuracy for a 3-way classification (NC vs. MI vs. SI) was approximately 71% for both tests; no significant difference was found between them. Conclusions The two drawing tests showed good performance for predicting severe impairment of cognition; however, a drawing test alone is not enough to predict overall CI. There are some limitations to our study: the sample size was small, all the participants did not perform both the CDT and RCFT-copy, and only the copy condition of the RCFT was used. Algorithms involving memory performance and longitudinal changes are worth future exploration. These results may contribute to improved home-based healthcare delivery.

Abstract Although cranial autonomic symptoms (CAS) are typical in cluster headache (CH), some individuals with CH show no CAS during their headache attacks. Probable cluster headache (PCH) is a subtype of CH that fulfils all but one criterion of CH. This study aimed to investigate the frequency and clinical features of CH and PCH without CAS in comparison to those with CAS. We analysed data from the Korea Cluster Headache Registry, a prospective multicentre registry involving data from 16 hospitals. Of the 216 participants with CH and 26 with PCH, 19 (8.8%) and 7 (26.9%), respectively, did not have CAS. Participants with CH without CAS exhibited less severe anxiety (General Anxiety Disorder-7 score, median [interquartile range], 2.0 [1.0–6.0] vs 8.0 [3.0–12.0], p = 0.001) and depression (Patient Health Questionnaire-9 score, 3.0 [1.0–7.0] vs 7.0 [3.0–11.0], p = 0.042) than those with CAS. Among participants with PCH, headache intensity was less severe in participants without CAS than in those with CAS (numeric rating scale, 8.0 [7.0–8.0] vs 9.5 [8.0–10.0], p = 0.015). In conclusion, a significant proportion of participants with CH and PCH did not have CAS. Some clinical features of CH and PCH differed based on the presence of CAS.

We investigated the effects of atherosclerosis in the carotid region on cerebral haemodynamics. A total of 15 stenosis cases following NASCET criteria were modelled using patient-specific medical image data and an open-source package, SimVascular. The formulation adopted the stabilised Petrov–Galerkin scheme with Newtonian and incompressible assumptions. The boundary conditions employed pulsatile inflow and three-element lumped Windkessel outlet conditions with a rigid wall assumption. We present transitions in the represented CoW during stenosis progression using three-dimensional aortic-cerebral vasculature for the first time. This was driven by the conserved total cerebral blood flow to 50% carotid stenosis (CS) (P-value, P > 0.05), which deteriorated during subsequent stages of CS (P < 0.01), and the effective collateral capability of the communicating arteries (CoAs) activated from a degree of 75% and above (P < 0.0001). The prevalence of ‘complete’ CoW peaked at 50% CS and then declined. Despite the collateral flow, the ipsilateral hemispheric perfusion was moderately reduced (P < 0.01), and the contralateral perfusion was conserved (P > 0.05), revealing the ineffectiveness of collateral capability of CoW at the extreme stages of CS. We identified bulk cerebral auto-regulation effects of the conventional Windkessel model, demonstrating accurate flow reduction in the stenosed artery.

Background Unlike patients with stroke caused by other mechanisms, the effect of elevated plasma total homocysteine (tHcy) on the prognosis of patients with both ischemic stroke and atrial fibrillation (AF) is unknown. This study aimed to evaluate the association between tHcy level and the functional outcome of patients with AF‐related stroke. Methods and Results We included consecutive patients with AF‐related stroke between 2013 and 2015 from the registry of a real‐world prospective cohort from 11 large centers in South Korea. A 3‐month modified Rankin Scale score ≥3 was considered an unfavorable outcome. Since tHcy is strongly affected by renal function, we performed a subgroup analysis according to the presence of renal dysfunction. A total of 910 patients with AF‐related stroke were evaluated (mean age, 73 years; male sex, 56.0%). The mean tHcy level was 11.98±8.81 μmol/L. In multivariable analysis, the tHcy level (adjusted odds ratio, 1.04; 95% CI, 1.01–1.07, per 1 μmol/L) remained significantly associated with unfavorable outcomes. In the subgroup analysis based on renal function, tHcy values above the cutoff point (≥14.60 μmol/L) showed a close association with the unfavorable outcome only in the normal renal function group (adjusted odds ratio, 3.10; 95% CI, 1.60–6.01). In patients with renal dysfunction, tHcy was not significantly associated with the prognosis of AF‐related stroke. Conclusions A higher plasma tHcy level was associated with unfavorable outcomes in patients with AF‐related stroke. This positive association may vary according to renal function but needs to be verified in further studies.

Abstract Background Our aim was to investigate the relationship between coexisting cluster headache (CH) and migraine with anxiety and depression during active cluster bouts, and how symptoms change during remission. Methods We analyzed data from 222 consecutive CH patients and 99 age- and sex-matched controls using a prospective multicenter registry. Anxiety or depression was evaluated using the Generalized Anxiety Disorder-7 (GAD-7) or Patient Health Questionnaire-9 (PHQ-9), respectively. Moderate-to-severe anxiety or depression was defined as a score of ≥10 at baseline (during a cluster bout). We assessed for changes in anxiety and depression during CH remission periods. Results Among the CH patients, the prevalence of moderate-to-severe anxiety and depression was seen in 38.2% and 34.6%, respectively. Compared with controls, CH patients were associated with moderate-to-severe anxiety and depression (multivariable-adjusted odds ratio [aOR] = 7.32, 95% confidence intervals [CI] = 3.35–15.99 and aOR = 4.95, 95% CI = 2.32–10.57, respectively). CH patients with migraine were significantly more likely to have moderate-to-severe anxiety and depression (aOR = 32.53, 95% CI = 6.63–159.64 and aOR = 16.88, 95% CI = 4.16–68.38, respectively), compared to controls without migraine. The GAD-7 and PHQ-9 scores were significantly reduced between cluster bout and remission periods (from 6.8 ± 5.6 to 1.6 ± 2.8; P

ObjectiveCluster headache (CH) is a rare, primary headache disorder, characterized of excruciating, strictly one-sided pain attacks and ipsilateral cranial autonomic symptoms. Given the debilitating nature of CH, delayed diagnosis can increase the disease burden. Thus, we aimed to investigate the diagnostic delay, its predictors, and clinical influence among patients with CH.MethodsData from a prospective multicenter CH registry over a 4-year period were analyzed. CH was diagnosed according to the International Classification of Headache Disorders (ICHD)-3 criteria, and diagnostic delay of CH was assessed as the time interval between the year of the first onset and the year of CH diagnosis. Patients were classified into three groups according to the tertiles of diagnostic delay (1st tertile, 40 years) belonged to the third tertile (9.0%). For year of onset, the proportion of patients in the 3rd tertile was the highest for the groups before the publication year of the ICHD-2 (74.7%) and the lowest for the groups after the publication year of the ICHD-3 beta version (0.5%). Compared with the first CH, episodic CH [multivariable-adjusted odds ratio (aOR) = 5.91, 95% CI = 2.42–14.48], chronic CH (aOR = 8.87, 95% CI = 2.66–29.51), and probable CH (aOR = 4.12, 95% CI = 1.48–11.43) were associated with the tertiles of diagnostic delay. Age of onset (aOR = 0.97, 95% CI = 0.95–0.99) and PHQ-9 score (aOR = 0.96, 95% CI = 0.93–0.99) were inversely associated with the tertile of diagnostic delay. The prevalence of suicidal ideation was highest in the patients of the third tertile. The mean HIT-6 score increased significantly with the diagnostic delay (p = 0.041).ConclusionsPatients with a younger onset of CH have a higher risk of diagnostic delay. Nevertheless, the rate of delayed diagnosis gradually improved over time and with the publication of the ICHD criteria, supporting the clinical significance of diagnostic clinical criteria and headache education to reduce the disease burden of CH.

Background: Ischemic stroke with atrial fibrillation (AF) may recur despite appropriate treatment. It may be AF-related or AF-unrelated. We compared the factors associated with AF-related and AF-unrelated recurrences among ischemic stroke patients with AF.Methods: Patients with ischemic stroke and AF were enrolled from 11 centers in Korea. Ischemic stroke recurrence was classified as AF-related if the lesion pattern was compatible with cardioembolism without significant stenosis or as AF-unrelated if the lesion was more likely due to small vessel disease or arterial stenosis. Factors associated with stroke recurrence (AF-related and AF-unrelated) were investigated.Results: Among the 2,239 patients, 115 (5.1%) experienced recurrence (75 AF-related and 40 AF-unrelated). Factors independently associated with any stroke recurrence included AF diagnosed before stroke, small subcortical infarctions, and small scattered lesions in a single vascular territory. Type of AF was associated with the type of stroke recurrence, with persistent AF being associated with AF-related stroke [hazard ratio (HR) = 2.94, 95% confidence interval (CI) 1.69–5.26; p < 0.001]. By contrast, paroxysmal AF (HR = 3.76, 95% CI 1.56–9.04; p = 0.003), AF diagnosed before stroke (HR = 2.38, 95% CI 1.19–4.55; p = 0.014), small scattered lesions in a single vascular territory (reference: corticosubcortical lesion, HR = 3.19, 95% CI 1.18–8.63; p = 0.022), and the use of antiplatelet agents (HR = 2.11, 95% CI 1.11–4.03; p = 0.024) were independently associated with AF-unrelated stroke.Conclusion: Persistent AF was more associated with AF-related stroke recurrence, whereas paroxysmal AF was more associated with AF-unrelated stroke recurrence. A scattered lesion in a single vascular territory may predict AF-unrelated stroke recurrence.

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.

Background: Although the frequency and intensity of headaches decrease in older adults, headaches in this population are still an important neurological disorder. The purpose of this study was to investigate the associations of headache characteristics in older adults with the development of cardiovascular disease and cognitive dysfunction. Methods: We prospectively enrolled 125 older (≥ 65 years old) patients with headache who were making their first visit to outpatient clinics and who had no prior history of cognitive dysfunction from 11 hospitals in Korea between August 2014 and February 2015. We investigated the occurrence of newly developed/or recurrent headache, cardiovascular disease, cognitive dysfunction, and poor functional outcomes. Results: The mean age of all included patients was 72.6 years, 68.8% were women, and 43 (34.4%) had newly developed/or recurrent headache during follow-up. During a median follow-up of 31 months (interquartile range, 28–34 months), 21 participants (16.8%) experienced cardiovascular disease, and 26 (20.8%) developed cognitive dysfunction. Upon multivariate analysis and after adjusting for sex, age, and other factors, presence of newly developed/or recurrent headache was found to be associated with cardiovascular disease (hazard ratio [HR], 4.03; 95% confidence interval [CI], 1.28–12.61; p=0.017) and frequency of headache for the recent 3 months was related with cognitive dysfunction (HR, 1.05; 95% CI, 1.00–1.09; p=0.017) and poor functional outcomes (HR, 1.06; 95% CI, 1.01–1.11; p=0.011). Conclusion: Our study demonstrated that there is an increased risk of cardiovascular disease, cognitive dysfunction, and poor functional outcomes in older patients with frequent, newly developed, or recurrent headache.

Abstract Objective We investigated the effect of arterial stiffness on the severity of enlarged perivascular spaces (EPVSs) and cerebral microbleeds (CMBs) at different brain locations. Methods A total of 854 stroke patients underwent both brachial‐ankle pulse wave velocity (baPWV) measurement and brain MRI. The extent of EPVS was separately rated at the levels of the basal ganglia (BG) and centrum semiovale (CS). The CMBs were categorized as strictly lobar CMB and deep CMB. The patients were categorized according to baPWV quartiles, and multivariable logistic regressions were performed to evaluate whether the baPWV increment was independently associated with each cerebral SVD marker at different locations. The odds ratio (OR) with 95% confidence interval (CI) was derived on the reference of the first quartile. Results Severe EPVSs at BG and CS were detected in 243 (28.5%) and 353 patients (41.3%), respectively. The increment of baPWV quartiles was associated with both severe BG EPVS burden (Q4: OR = 2.58, CI = 1.45–4.60) and severe CS EPVS burden (Q4: OR = 2.06, CI = 1.24–3.42). Deep CMBs were found in 259 patients (30.3%), and strictly lobar CMBs were found in 170 patients (19.9%). Multivariable logistic regression model revealed deep CMB was independently associated with the baPWV increment (Q4: OR = 2.52, CI = 1.62–3.94). However, strictly lobar CMB had a neutral relationship with baPWV. Conclusion Increased arterial stiffness is consistently associated with the presence of deep CMB and severe EPVS burden at the BG and CS, suggesting a common pathophysiologic mechanism.

BACKGROUND:Identifying acute ischemic stroke (AIS) among potential stroke cases is crucial for stroke research based on claims data. However, the accuracy of using the diagnostic codes of the International Classification of Diseases 10th revision was less than expected. METHODS:From the National Health Insurance Service (NHIS) claims data, stroke cases admitted to the hospitals participating in the multicenter stroke registry (Clinical Research Collaboration for Stroke in Korea, CRCS-K) during the study period with principal or additional diagnosis codes of I60-I64 on the 10th revision of International Classification of Diseases were extracted. The datasets were randomly divided into development and validation sets with a ratio of 7:3. A stroke identification algorithm using the claims data was developed and validated through the linkage between the extracted datasets and the registry database. RESULTS:Altogether, 40,443 potential cases were extracted from the NHIS claims data, of which 31.7% were certified as AIS through linkage with the CRCS-K database. We selected 17 key identifiers from the claims data and developed 37 conditions through combinations of those key identifiers. The key identifiers comprised brain CT, MRI, use of tissue plasminogen activator, endovascular treatment, carotid endarterectomy or stenting, antithrombotics, anticoagulants, etc. The sensitivity, specificity, and diagnostic accuracy of the algorithm were 81.2%, 82.9%, and 82.4% in the development set, and 80.2%, 82.0%, and 81.4% in the validation set, respectively. CONCLUSIONS:Our stroke identification algorithm may be useful to grasp stroke burden in Korea. However, further efforts to refine the algorithm are necessary.

Abstract Background Cluster headaches (CH) are recurrent severe headaches, which impose a major burden on the life of patients. We investigated the impact of CH on employment status and job burden. Methods The study was a sub-study of the Korean Cluster Headache Registry. Patients with CH were enrolled from September 2016 to February 2018 from 15 headache clinics in Korea. We also enrolled a headache control group with age-sex matched patients with migraine or tension-type headache. Moreover, a control group including individuals without headache complaints was recruited. All participants responded to a questionnaire that included questions on employment status, type of occupation, working time, sick leave, reductions in productivity, and satisfaction with current occupation. The questionnaire was administered to participants who were currently employed or had previous occupational experience. Results We recruited 143 patients with CH, 38 patients with other types of headache (migraine or tension-type headache), and 52 headache-free controls. The proportion of employees was lower in the CH group compared with the headache and headache-free control groups (CH: 67.6% vs. headache controls: 84.2% vs. headache-free controls: 96.2%; p = 0.001). The CH group more frequently experienced difficulties at work and required sick leave than the other groups (CH: 84.8% vs. headache controls: 63.9% vs. headache-free controls: 36.5%; p

Background There is insufficient evidence on the effect of statins, particularly high‐intensity statins, in patients with acute ischemic stroke and atrial fibrillation. We investigated the impact of statins on the outcomes in these patients, including those who might be vulnerable to statin therapy and those without clinical atherosclerotic cardiovascular diseases. Methods and Results A total of 2153 patients with acute ischemic stroke and atrial fibrillation were enrolled in the present nationwide, multicenter, cohort study. The primary composite end point was the occurrence of net adverse clinical and cerebral events (NACCE; death from any cause, stroke, acute coronary syndrome, or major bleeding) over a 3‐year period based on statin intensity. NACCE rates were lower in patients receiving low‐ to moderate‐intensity (adjusted hazard ratio 0.64; 95% CI: 0.52‐0.78) and high‐intensity statins (hazard ratio 0.51; 95% CI 0.40‐0.66) than in those not receiving statin therapy. High‐intensity statins were associated with a lower risk for NACCE than low‐ to moderate‐intensity statins (hazard ratio 0.76; 95% CI 0.59‐0.96). Subgroup analyses showed that the differences in hazard ratio for 3‐year NACCE favored statin use across all subgroups, including older patients, those with low cholesterol levels, patients receiving anticoagulants, and patients without clinical atherosclerotic cardiovascular diseases. Magnified benefits of high‐intensity statins compared with low‐ to moderate‐intensity statins were observed in patients who underwent revascularization therapy and those under 75 years of age. Conclusions Statins, particularly high‐intensity statins, could reduce the risk for NACCE in patients with acute ischemic stroke and atrial fibrillation; this needs to be further explored in randomized controlled trials.

Abstract Background Cluster headache is famous for attacks with seasonal and diurnal periodicity. This diurnal and seasonal variation might be related to sunlight and vitamin D metabolism. We investigated the serum vitamin D levels in patients with cluster headache. Methods We enrolled patients with cluster headache and age- and sex-matched migraineurs and normal controls. From October 2016 to March 2018, non-fasting serum 25(OH)D concentrations were measured using a chemiluminescent immunoassay. Vitamin D deficiency was defined as a concentration

Choline alphoscerate in clinical studies improved cognitive dysfunction in dementia, but it did not show any clear clinical benefit on mild cognitive impairment (MCI). There is limited evidence of neuropsychological markers in showing the effects of cholinergic precursors in MCI. Object of this preliminary study is to evaluate the change of the P300 latency as a biomarker for cognitive function after taking choline alphoscerate in patients with MCI. Event related evoked potential study were done in baseline (n = 27) and 3 months after taking choline alphoscerate (n = 17). When compared to our previous reported control database, the difference of the P300 latencies between MCI and control group at baseline was statistically significant (P

The criterion for the remission period of chronic cluster headache (CCH) was recently revised from < 1 month to < 3 months in the third edition of the International Classification of Headache Disorders (ICHD-3). However, information on the clinical features of CCH based on the ICHD-3 criteria is currently limited. The present study aimed to investigate the clinical features of CCH based on ICHD-3 using data from the Korean Cluster Headache Registry (KCHR). The KCHR is a multicentre prospective registry of patients with cluster headache (CH) from 15 hospitals. Among the 250 participants with CH, 12 and 176 participants were classified as having CCH and episodic cluster headache (ECH), respectively. Among 12 participants with CCH, 6 (50%) had remission periods of < 1 month, and the remaining 6 (50%) had a remission period of 1-3 months. Six participants had CCH from the time of onset of CH, and in the other 6 participants, CCH evolved from ECH. CCH subjects had later age of onset of CH, developed the condition after a longer interval after CH onset, and had more migraine and less nasal congestion and/or rhinorrhoea than ECH subjects. Clinical features of CCH with remission periods < 1 month were not significantly different from those of CCH with remission periods of 1-3 months, except for the total number of bouts. More current smoking and less diurnal rhythmicity were observed in participants with CCH evolved from ECH compared to those with ECH. In conclusion, the number of subjects with CCH doubled when the revised ICHD-3 criteria were used. Most of clinical characteristics of CCH did not differ when the previous and current version of ICHD was applied and compared. Some clinical features of CCH were different from those of ECH, and smoking may have a role in CH chronification.

Background: Epidemiological data of probable cluster headaches (CH) are scarce in the relevant literature. Here, we sought to assess the prevalence and clinical characteristics of probable CH in comparison with definite CH.Methods: Data used in this study were obtained from the Korean Cluster Headache Registry (KCHR), a prospective, cross-sectional, multicenter headache registry that collected data from consecutive patients diagnosed with CH.Results: In total, 159 patients were enrolled in this study; 20 (12.6%) were diagnosed with probable CH. The most common unfulfilled criterion in patients with probable CH was the duration of attack, which was found in 40% of patients with probable CH. Among clinical characteristics, the number of autonomic symptoms tended to be lower in probable CH than in definite CH (1.7 ± 1.2 vs. 2.4 ± 1.5, p = 0.051) and conjunctival injection and lacrimation showed an increased odds ratio (OR) [OR = 3.03; 95% confidence interval (CI): 1.03–8.33] in definite CH. The groups did not differ with regard to baseline demographic characteristics, disability, impact on life, or treatment response.Conclusions: Probable CH is relatively common among CH disorders, with a clinical impact similar to that of definite CH.

Background Thrombi retrieved from patients with acute ischemic stroke may contain prognostic information. Objective: To investigate the relationship between the immunologic phenotype of thrombi and future vascular events in patients with a stroke. Methods This study included patients with acute ischemic stroke who underwent endovascular thrombectomy at Chung-Ang University Hospital in Seoul, Korea, between February 2017 and January 2020. Laboratory and histological variables were compared between patients with and without recurrent vascular events (RVEs). Kaplan-Meier analysis followed by the Cox proportional hazards model was used to identify factors related to RVE. Receiver operating characteristic (ROC) analysis was conducted to evaluate the performance of the immunologic score by combining immunohistochemical phenotypes to predict RVE. Results A total of 46 patients were included in the study with 13 RVEs (mean±SD age, 72.8±11.3 years; 26 (56.5%) men). Thrombi with a lower percentage of programmed death ligand-1 expression (HR=11.64; 95% CI 1.60 to 84.82) and a higher number of citrullinated histone H3 positive cells (HR=4.19; 95% CI 0.81 to 21.75) were associated with RVE. The presence of high-mobility group box 1 positive cell was associated with reduced risk of RVE, but the association was lost after adjustment for stroke severity. The immunologic score, which consists of the three immunohistochemical phenotypes, showed good performance in predicting RVE (area under the ROC curve, 0.858; 95% CI 0.758 to 0.958). Conclusions The immunological phenotype of thrombi could provide prognostic information after stroke. [ABSTRACT FROM AUTHOR]

Background We investigated the microRNA expression pattern from thrombus retrieved by mechanical thrombectomy in acute stroke patients to understand the stroke mechanism. Methods This 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. Results In 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. Conclusions The 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. [ABSTRACT FROM AUTHOR]

Purpose: Non-vitamin K antagonist oral anticoagulants (NOACs) are widely used in patients with atrial fibrillation (AF) because of their effectiveness in preventing stroke and their better safety, compared with warfarin. However, there are concerns for an increased risk of bleeding associated with concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) or selective serotonin reuptake inhibitors (SSRIs) with NOACs. In this study, we aimed to evaluate the risk of bleeding events in individuals taking concomitant NSAIDs or SSRIs with NOACs after being diagnosed with AF. Materials and Methods: A nested case-control analysis to assess the safety of NSAIDs and SSRIs among NOAC users with AF was performed using data from Korean National Health Insurance Service from January 2012 to December 2017. Among patients who were newly prescribed NOACs, 1233 cases hospitalized for bleeding events were selected, and 24660 controls were determined. Results: The risk of bleeding events was higher in patients receiving concomitant NSAIDs [adjusted odds ratio (aOR) 1.41; 95% confidence interval (CI) 1.24-1.61] or SSRIs (aOR 1.92; 95% CI 1.52-2.42) with NOACs, compared to no use of either drug, respectively. The risk of upper gastrointestinal bleeding was higher in patients receiving concomitant NSAIDs or SSRIs without proton pump inhibitors (PPIs) (NSAIDs: aOR 2.47; 95% CI 1.26-4.83, SSRI: aOR 10.8; 95% CI 2.41-2.48) compared to no use. Conclusion: When NSAIDs or SSRIs are required for NOAC users with AF, physicians need to monitor bleeding events and consider the use of PPIs, especially for combined use of both drugs or when initiating NOACs treatment. [ABSTRACT FROM AUTHOR]

Background: Although the frequency and intensity of headaches decrease in older adults, headaches in this population are still an important neurological disorder. The purpose of this study was to investigate the associations of headache characteristics in older adults with the development of cardiovascular disease and cognitive dysfunction. Methods: We prospectively enrolled 125 older (≥ 65 years old) patients with headache who were making their first visit to outpatient clinics and who had no prior history of cognitive dysfunction from 11 hospitals in Korea between August 2014 and February 2015. We investigated the occurrence of newly developed/or recurrent headache, cardiovascular disease, cognitive dysfunction, and poor functional outcomes. Results: The mean age of all included patients was 72.6 years, 68.8% were women, and 43 (34.4%) had newly developed/or recurrent headache during follow-up. During a median follow-up of 31 months (interquartile range, 28-34 months), 21 participants (16.8%) experienced cardiovascular disease, and 26 (20.8%) developed cognitive dysfunction. Upon multivariate analysis and after adjusting for sex, age, and other factors, presence of newly developed/or recurrent headache was found to be associated with cardiovascular disease (hazard ratio [HR], 4.03; 95% confidence interval [CI], 1.28-12.61; p=0.017) and frequency of headache for the recent 3 months was related with cognitive dysfunction (HR, 1.05; 95% CI, 1.00-1.09; p=0.017) and poor functional outcomes (HR, 1.06; 95% CI, 1.01-1.11; p=0.011). Conclusion: Our study demonstrated that there is an increased risk of cardiovascular disease, cognitive dysfunction, and poor functional outcomes in older patients with frequent, newly developed, or recurrent headache. [ABSTRACT FROM AUTHOR]

Background: Glycogen phosphorylase is the key enzyme that breaks down glycogen to yield glucose-1-phosphate in order to restore depleted energy stores during cerebral ischaemia. We sought to determine whether plasma levels of glycogen phosphorylase BB (GPBB) isoform increased in patients with acute ischaemic stroke (AIS).Methods: We studied plasma GPBB levels within 12 hours and again at 48±24 hours of symptom onset in 172 patients with imaging-confirmed AIS and 133 stroke-free individuals. We determined the ability of plasma GPBB to discriminate between cases and controls and examined the predictive value of plasma GPBB for 90-day functional outcome, 90-day survival and acute lesion volumes on neuroimaging.Results: The mean (SD) GPBB levels were higher in cases (46.3±38.6 ng/mL at first measurement and 38.6±36.5 ng/mL at second measurement) than in controls (4.1±7.6 ng/mL, p<0.01 for both). The area under the receiver operating characteristic (ROC) curve for case-control discrimination based on first GPBB measurement was 0.96 (95% CI 0.93 to 0.98). The sensitivity and specificity based on optimal operating point on the ROC curve (7.0 ng/mL) were both 93%. GPBB levels increased in 90% of patients with punctate infarcts (<1.5 mL) and in all patients admitted within the first 4.5 hours of onset. There was no correlation between GPBB concentration and either clinical outcome or acute infarct volume.Conclusion: GPBB demonstrates robust response to acute ischaemia and high sensitivity for small infarcts. If confirmed in more diverse populations that also include stroke mimics, GPBB could find utility as a stand-alone marker for acute brain ischaemia. [ABSTRACT FROM AUTHOR]