Background: Cerebral microbleeds are known to be indicative of bleeding-prone microangiopathy and may predict incident intracerebral hemorrhage (ICH). In this study, we investigated whether microbleeds are associated with the incidence of warfarin-related ICH. Methods: Twenty-four patients with ICH while on outpatient treatment with warfarin were selected from a consecutive cohort. Control, warfarin-using subjects with no history of ICH were randomly selected during the same time period (n = 48). We compared demographic factors, vascular risk factors, laboratory findings, and radiologic findings including microbleeds between the groups. Result: There were more cases of patients with microbleeds in the ICH than control group (79.2% vs 22.9%: p < 0.001), and the number of microbleeds was much higher for the ICH group (9.0 ± 26.8 vs 0.5 ± 1.03: p < 0.001). Moreover, the number of microbleeds was significantly correlated with the presence of warfarin-related ICH (r = 0.299; p < 0.001). Conditional logistic regression analysis showed that increased prothrombin time and the presence of microbleeds were independently related to the incidence of warfarin-related ICH (microbleeds: adjusted OR, 83.12). Conclusion: This study suggests that underlying microbleeds are independently associated with an incidence of warfarin-related intracerebral hemorrhage. Future research should focus on elucidating the risks and benefits of warfarin medication in patients with microbleeds.

Background: Preclinical data suggest circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with inactive phase (daytime) than active phase (nighttime) stroke onset. We aimed to examine the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke.Methods and findings: In a Korean nationwide multicenter observational cohort study from May 2011 to July 2020, we assessed circadian effects on initial stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at admission), END, and favorable functional outcome (3-month modified Rankin Scale [mRS] score 0 to 2 versus 3 to 6). We included 17,461 consecutive patients with witnessed ischemic stroke within 6 hours of onset. Stroke onset time was divided into 2 groups (day-onset [06:00 to 18:00] versus night-onset [18:00 to 06:00]) and into 6 groups by 4-hour intervals. We used mixed-effects ordered or logistic regression models while accounting for clustering by hospitals. Mean age was 66.9 (SD 13.4) years, and 6,900 (39.5%) were women. END occurred in 2,219 (12.7%) patients. After adjusting for covariates including age, sex, previous stroke, prestroke mRS score, admission NIHSS score, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, prestroke antiplatelet use, prestroke statin use, revascularization, season of stroke onset, and time from onset to hospital arrival, night-onset stroke was more prone to END (adjusted incidence 14.4% versus 12.8%,p= 0.006) and had a lower likelihood of favorable outcome (adjusted odds ratio, 0.88 [95% CI, 0.79 to 0.98];p= 0.03) compared with day-onset stroke. When stroke onset times were grouped by 4-hour intervals, a monotonic gradient in presenting NIHSS score was noted, rising from a nadir in 06:00 to 10:00 to a peak in 02:00 to 06:00. The 18:00 to 22:00 and 22:00 to 02:00 onset stroke patients were more likely to experience END than the 06:00 to 10:00 onset stroke patients. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, falling from a peak at 06:00 to 10:00 to a nadir at 22:00 to 02:00. Study limitations include the lack of information on sleep disorders and patient work/activity schedules.Conclusions: Night-onset strokes, compared with day-onset strokes, are associated with higher presenting neurologic severity, more frequent END, and worse 3-month functional outcome. These findings suggest that circadian time of onset is an important additional variable for inclusion in epidemiologic natural history studies and in treatment trials of neuroprotective and reperfusion agents for acute ischemic stroke.

Background: Obesity is believed to increase the risks of ischemic stroke or coronary heart disease; however, regarding outcome after established vascular diseases, recent unexpected evidence has suggested that an increased body mass index (BMI) might have beneficial effects (obesity paradox). The aim of this study was to evaluate the independent association between BMI and long-term mortality after ischemic stroke. Methods: A total of 1,592 consecutive patients with ischemic stroke were prospectively included through our stroke cohort. In this study, the levels of BMI were classified based on guidelines for the Asian-Pacific population. Initial neurological severity was estimated by the National Institutes of Health Stroke Scale (NIHSS) score. Information on mortality was collected until the end of 2009, and the median follow-up period was 4 years. To examine the association between BMI and long-term mortality, we used Cox’s proportional regression analysis. Results: During follow-up, 23% of patients died. Linear regression analysis showed that the level of BMI was inversely related to initial neurological severity (p = 0.002). In the model of adjustment of age and gender using Cox’s proportional regression analysis, this inverse trend was also significant (reference, normal weight; hazard ratio of underweight, 2.45; overweight, 0.77; obesity, 0.60). However, after adjustment of all covariates, including initial neurological severity, only the harmful effect of underweight remained significant (2.79; 95% CI, 1.92–4.05); however, beneficial effects of overweight and obesity did not. Conclusion: Our study showed that an independent association between BMI and long-term mortality after ischemic stroke was found only in underweight patients. The obesity paradox phenomenon seems to be limited, and might not be interpreted as a direct causal relationship due to a strong association with initial neurological severity.

Human enterovirus 71 (EV 71) has caused large-scale outbreaks of hand-foot-and-mouth disease (HFMD), particularly in the Asian-Pacific region. In this study, we report a major outbreak of EV 71 infection in Korea and describe the clinical differences between EV 71 and non-EV 71 enterovirus infections. We prospectively enrolled patients with suspected viral infections during a recent 2-year period through a nationwide surveillance system. We identified 719 patients with suspected HFMD or herpangina using real-time PCR and genotyping based on VP1 sequence analysis. The major pathogen causing HFMD changed substantially from 2008 to 2009, with EV 71 becoming the most common cause of HFMD in Korea in 2009. We successfully identified the enteroviral genotypes for 218 of the 719 patients. Patients with EV 71 infections tended to be younger than those with non-EV 71 enteroviral infections and presented with HFMD and meningoencephalitis. In addition, the occurrence of fever, headache, and neck stiffness was significantly higher in patients with EV 71 infections. Multivariable analysis showed that for patients presenting with HFMD, fever, or a sore throat, each covariate was independently associated with EV 71 infection; the adjusted odds ratios (with 95% confidence intervals in parentheses) for these variables were 31.86 (10.04 to 101.09), 4.76 (1.71 to 13.25), and 0.18 (0.04 to 0.77), respectively. Our results indicate that EV 71 was a major cause of HFMD in Korea during the study period. In addition, we found that clinical symptoms may be helpful in the early identification of patients with EV 71 infections.

Futile reperfusion (poor functional status despite successful reperfusion) was observed in up to 67% of patients enrolled in recent endovascular treatment (EVT) clinical trials. We investigated the impact of baseline stroke severity on both futile reperfusion and therapeutic benefit of successful EVT. Using a prospective multicenter stroke registry, we identified consecutive ischemic stroke patients with anterior circulation large artery occlusion, who were reperfused successfully by EVT (Thrombolysis in Cerebral Infarction grade 2b–3). The rate of futile reperfusion was assessed across the initial National Institutes of Health Stroke Scale (NIHSS) scores. The frequency of poor outcomes (modified Rankin scale [mRS] 3–6) according to NIHSS scores was compared between patients revascularized successfully by EVT and those who did not receive EVT, after standardizing for age. Among 21,591 patients with ischemic stroke, 972 (4.5%) received EVT within 12 h of onset, including 440 who met study eligibility criteria. Futile reperfusion was observed in 226 of the 440 study-eligible patients (51.4%) and was associated with stroke severity: 20.9% in NIHSS scores ≤5, 34.6% in 6–10, 58.9% in 11–20, and 63.8% in > 20 (p < 0.001). Nonetheless, the therapeutic benefit of EVT also increased with increasing stroke severity (p for interaction < 0.001): 0.1% in NIHSS ≤5, 18.6% in 6–10, 28.7% in 11–20, and 34.3% in > 20. EVT is more beneficial with increasing stroke severity, although futile reperfusion also increases with higher stroke severity.