Background and Purpose—: The relationship between the dose of recombinant tissue-type plasminogen activator (r-tPA) and its safety/efficacy for ischemic stroke has not been well evaluated in the East Asian population. We assessed the safety/efficacy of different doses of r-tPA for acute ischemic stroke in Chinese patients. Methods—: A total of 1004 eligible patients were classified according to the dose of r-tPA received for managing acute ischemic stroke: 0.9 mg/kg (n=422), 0.8 mg/kg (n=202), 0.7 mg/kg (n=199), and 0.6 mg/kg (n=181). The safety outcome was symptomatic intracerebral hemorrhage and death within 3 months. The efficacy outcome was good functional outcome (modified Rankin Scale ≤1) at 3 months. Results—: There was a significant trend for symptomatic intracerebral hemorrhage with age ( P =0.002). With multivariate logistic regression analysis, a dose of 0.9 mg/kg was a predictor of symptomatic intracerebral hemorrhage ( P =0.0109), and a dose ≤0.65 mg/kg was a predictor of good functional outcome ( P =0.0369). In patients aged 71 to 80 years, there was a significant trend of increasing symptomatic intracerebral hemorrhage ( P =0.0130) and less good functional outcome ( P =0.0179) with increasing doses of r-tPA. There was also a trend of increasing mortality ( P =0.0971) at 3 months in these patients. Conclusions—: These results did not support the dose of 0.9 mg/kg of r-tPA being optimal for all patients in the East Asian population. In elderly patients (71–80 years), a lower dose of 0.6 mg/kg is associated with a better outcome. Confirmation of the results through randomized trial is required.

Background: The triglyceride-glucose (TyG) index has recently been proposed as a reliable marker of insulin resistance. There is insufficient evidence to verify that the TyG index is correlated with functional outcomes and hemorrhagic transformation and in patients with stroke treated with intravenous thrombolysis (IVT).Methods: We designed a multicenter cohort study, which enrolled patients with acute ischemic stroke treated with IVT between December 2004 and December 2016. The TyG index was divided into tertiles and calculated on a continuous scale. Unfavorable functional outcomes were defined by the modified Rankin Scale of 3–6 at 90 days and the incident rates of symptomatic intracranial hemorrhage (SICH) within 36 h of IVT onset were surveyed. Stroke severity was defined as mild (4–8), moderate (9–15), or high (≥16) based on the National Institutes of Health Stroke Scale (NIHSS) scores.Results: Among 914 enrolled patients, the tertiles of the TyG index were 8.48 for T1, 8.48–9.04 for T2, and 9.04 for T3. T3 showed an increased risk of unfavorable functional outcomes at 90 days [odds ratio (OR): 1.76; P = 0.0132]. The TyG index was significantly associated with unfavorable functional outcomes at 90 days (OR: 1.32; P = 0.0431 per unit increase). No association was found between the TyG index and SICH. These findings were applicable for T3 with stroke of moderate (OR, 2.35; P = 0.0465) and high severity (OR: 2.57, P = 0.0440) patients with stroke.Conclusion: This study supports the strong association between the increased TyG index and increased unfavorable functional outcomes at 90 days in patients with acute ischemic stroke treated with IVT. These findings were found to be robust in patients with moderate and high stroke severity.

A vertebral artery (VA) terminating in a posterior inferior cerebellar artery (PICA) is often considered to be a normal variation associated with VA hypoplasia. We aimed to investigate the clinical significance of this cerebrovascular variant. A total of 80 patients with clinically evident cerebrovascular events in posterior circulation were examined by duplex sonography and magnetic resonance angiography (MRA). Eighty healthy subjects who had MRA check-up were recruited as controls. PICA termination of the VA (PICA-VA) was identified as the VA not communicating with the basilar artery (BA) but ending into a PICA. We compared the prevalence of PICA-VA and associated hemodynamic parameters between the patients with and without PICA-VA, and investigated their relationships with VA hypoplasia. The prevalence of PICA-VA was higher in the patient group than in the controls (18.7% vs. 6.3%, p = 0.015). Most measurements (73.3%) of PICA-VA did not fit the criteria of VA hypoplasia. In comparison with the non-PICA-terminating group, the PICA-VA has a smaller diameter (3.7 ± 0.7 mm vs. 3.0 ± 0.5 mm, p < 0.001), lower mean velocity (241 ± 100 mm/sec vs. 164 ± 88 mm/sec, p < 0.01), and higher pulsatility index (1.3 ± 0.5 vs. 1.9 ± 0.6, p < 0.001). Moreover, a smaller diameter of the BA (3.2 ± 0.5 mm vs. 2.5 ± 0.9 mm, p = 0.004) and the posterior cerebral artery (PCA) (2.0 ± 0.1 mm vs. 1.6 ± 0.1 mm, p = 0.006) were also noted in the PICA-VA group. The higher prevalence of PICA-VA in the patient group with smaller diameter of VA, BA and PCA reflected its clinical significance, suggesting that PICA-VA may have a detrimental impact on cerebral hemodynamics. However, the sample is small, and further studies are needed with larger sample size for confirmation.

The major pathological characteristics of Alzheimer’s disease (AD) include senile plaques and neurofibrillary tangles (NFTs), which are mainly composed of aggregated amyloid-beta (Aβ) peptide and hyperphosphorylated tau protein, respectively. The excessive production of reactive oxygen species (ROS) and neuroinflammation are crucial contributing factors to the pathological mechanisms of AD. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor critical for tissue adaption to low-oxygen tension. Growing evidence has suggested HIF-1 as a potential therapeutic target for AD; conversely, other experimental findings indicate that HIF-1 induction contributes to AD pathogenesis. These previous findings thus point to the complex, even contradictory, roles of HIF-1 in AD. In this review, we first introduce the general pathogenic mechanisms of AD as well as the potential pathophysiological roles of HIF-1 in cancer, immunity, and oxidative stress. Based on current experimental evidence in the literature, we then discuss the possible beneficial as well as detrimental mechanisms of HIF-1 in AD; these sections also include the summaries of multiple chemical reagents and proteins that have been shown to exert beneficial effects in AD via either the induction or inhibition of HIF-1.

Prolonged hospital stay and readmission are prevalent problems for stroke patients in Taiwan after the acute stage, partly due to the unmet need of post-acute care. In March 2014, Taiwan's National Health Insurance Administration launched a nationwide Post-Acute Care-CerebroVascular Disease (PAC-CVD) program. The Taiwan Stroke Society, coordinating 11 allied disciplines, took responsibility for the preparation and implementation of the program. As of June 2016, 6839 consecutive stroke patients were enrolled. On discharge from the PAC program, the functional status had improved in 87.5% of patients, with a significant decrease in the mean modified Rankin Scale score from 3.7 to 3.0. The rates of readmission and mortality in the PAC group were also lower than in the control group. In conclusion, the Taiwan's PAC-CVD program is an innovative and essentially effective national program of post-acute stroke care. We believe such experience should be helpful for policy makers of stroke care worldwide.

Background: Previous neuroimaging and ultrasound studies suggested that compression and stenosis of the internal jugular vein (IJV) in patients with transient global amnesia (TGA) may impair IJV drainage, while a patent IJV releases intracranial pressure caused by the Valsalva maneuver (VM). Methods: Seventy-nine TGA patients with complete ultrasound examination data during admission were recruited prospectively to evaluate IJV drainage, which included the time-averaged mean velocity, and the cross-sectional lumen area of the IJV at the vein's middle (J2) and distal (J3) segments and the cross-sectional area during a 10-s VM to test for any retrograde or anti-grade flow. Forty-five TGA patients and 45 age- and sex-matched control subjects underwent complete contrast-enhanced magnetic resonance (MR) venous studies, which included time-resolved imaging of contrast kinetics, contrast-enhanced axial T1-weighted MR imaging, and phase-contrast-based non-contrast enhanced magnetic resonance venography (MRV). Results: In those subjects with complete MRV studies, the flow volumes exhibited at both the J2 and J3 segments of the left IJV and left vertebral vein (VV) were significantly lower in the TGA patients than in the control subjects. Although there was no significant difference in the flow volume of right IJV, the total of bilateral IJV, and VV flow volumes was still significantly lower in the TGA patients. As compared with the control subjects, the TGA patients exhibited significantly higher prevalence of completely blocked right IJV drainage at the J3 segment during the VM, but non-significantly higher for the left IJV at the J3 segment and for the right IJV at the J2 segment. Conclusion: Our results confirmed that the total venous flow decreases in the IJVs and VVs of the patients with TGA. This is consistent with the findings of previous MR imaging studies that have reported about compression and stenosis of the draining veins. We also found that IJV drainage is relatively compromised during the VM in the patients with TGA.