Chia-Yu Hsu

Genetic polymorphism of LDLR (rs688) is associated with primary intracerebral hemorrhage.

Intracranial hemorrhage is the third most common cause of cerebrovascular disease. Some polymorphisms that affect clotting factors increase the risk of thrombosis. However, few reports have analyzed the effect of polymorphisms on the hemostatic state in bleeding disorders. The low-density lipoprotein receptor (LDLR) has been shown to contribute to factor VIII (FVIII) homeostasis, which represents a link between LDLR and hemostasis. FVIII plays a pivotal role in the coagulation cascade. Patients with high levels of FVIII are at an increased risk of arterial and venous thrombosis. On the other hand, patients with insufficient FVIII tend to bleed excessively, such as in hemophilia A. In a previous study, analysis of the genetic LDLR variant rs688 provided evidence suggesting that genetic polymorphisms of rs688 are associated with thrombotic cardiovascular diseases. The current study aimed to investigate the potential role of rs688 in primary intracerebral hemorrhage (PICH). This genetic association study was conducted within an isolated Taiwanese population (447 PICH patients and 430 controls). Genotypes C/C and C/T were used as the reference genotypes, and the genotype T/T was found to be associated with a 73% decreased risk of PICH. The preliminary evidence suggests that genetic polymorphisms of LDLR are associated with PICH.

Hemodynamic Factors May Play a Critical Role in Neurological Deterioration Occurring within 72 hrs after Lacunar Stroke

Background Whether a perfusion defect exists in lacunar infarct and whether it is related to early neurological deterioration (END) is still under debate. The aim of this study was to evaluate whether END in lacunar infarct is related to a perfusion defect using diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI) and perfusion MR imaging. Methods One hundred and forty-one consecutive patients had an MRI scan within 30 hours after onset of symptoms and 43 patients with acute lacunar infarct and classic lacunar syndrome were recruited. The MRI sequences included DWI, DTI and cerebral blood flow (CBF) maps to respectively represent the topographic locations of acute infarcts, the corticospinal tract and perfusion defects. The END was defined in reference to the National Institute of Health Stroke Scale (NIHSS) as an increase ≧2 within 72 hours. Cohens Kappa coefficient was used to examine the reliability between the 2 image readers. A multivariate logistic regression model was constructed adjusting for baseline variables. Results Ten out of the 43 patients had END. Patients having END was significantly associated with lower chances of favorable and good outcomes at 3 months (pu200a=u200a0.01 and pu200a=u200a0.002, respectively). END was predicted when the non-core hypoperfused area overlapped on the corticospinal tract, which is defined as the expected END profile. Cohens Kappa coefficient between the 2 image readers to define images of expected END profiles was 0.74. In 15 patients with expected END profile, 9 had END clinically, whereas 28 patients had no expected END profile, and only 1 patient had END (p<0.0001). After adjusting for sex, the expected END profile was still associated with END (odds ratio, 42.2; pu200a=u200a0.002). Conclusion Our study demonstrated that the END in acute lacunar stroke is likely related to the transformation of non-core hypoperfused area into infarction in the anatomy of corticospinal tracts.

Comparisons of outcomes in stroke subtypes after intravenous thrombolysis

AbstractnThe purpose of this study was to analyze the outcomes and complications between stroke subtypes after intravenous thrombolysis. A total of 471 patients with acute ischemic stroke after intravenous thrombolysis from January 2007 to April 2014 were enrolled and classified according to the Trial of Org 10172 in Acute Stroke Treatment. A multivariate logistic regression model was used to evaluate the outcomes and complications among stroke subtypes after adjusting for baseline variables. Of the 471 patients, 117 (25.1xa0%) had large-artery atherosclerosis (LAA), 148 (31.8xa0%) had cardioembolism (CE), 82 (17.6xa0%) had small vessel disease (SVD), 119 (25.5xa0%) had undetermined etiology, and 5 (1.1xa0%) had other determined etiology. The patients with SVD had the mildest initial stroke severity and highest ratio of good and favorable outcomes, whereas those with CE had a higher rate of symptomatic intracranial hemorrhage (sICH) than those with SVD. After adjusting for confounding factors, the ratio of favorable outcome in the patients with SVD stroke was higher than in those with LAA. SVD was associated with a significantly lower rate of any hemorrhage compared to other stroke subtypes, whereas there were no differences in sICH or mortality between stroke subtypes. A lower initial National Institutes of Health Stroke Scale score was associated with good and favorable outcomes, and lower rates of sICH and mortality. The patients with SVD after intravenous thrombolysis had better outcomes and a lower rate of hemorrhage even after adjusting for confounding factors. Stroke severity was an independent factor associated with better functional outcomes, sICH and mortality.

Motor outcome of deep intracerebral haemorrhage in diffusion tensor imaging: comparison of data from different locations along the corticospinal tract

Abstract Objectives: Although diffusion tensor imaging (DTI) is widely studied to assess the motor outcome after ischaemic stroke, there is paucity of data regarding outcomes of intracerebral haemorrhage (ICH). The aim of this study was to determine the DTI data from different locations along the corticospinal tract (CST) and association to motor outcome. Methods: We prospectively recruited patients with deep ICH admitted to our hospital from November 2010 to July 2012.Diffusion tensor imaging was performed within 14u200adays after the onset of ICH. Fractional anisotropy (FA) was measured along the CST at corona radiata, perihaematomal oedema, cerebral peduncle and pons. Corticospinal tract integrity was classified into three types by diffusion tensor tractography (DTT): type A with preserved CST, type B with partially interrupted CST and type C with completely interrupted CST. Motor outcome was assessed by Motricity index (MI) at admission, after 1 and 3u200amonths. Results: Forty-eight patients were enrolled with a mean age of 62u200ayears. The median time interval from onset of ICH to DTI study was 7u200adays. The patients in type C had significantly worse MI at admission (Pu2009<u20090.001), after 1u200amonth (Pu2009<u20090.001) and after 3u200amonths (Pu2009<u20090.001) as compared to those with type A and type B. Lower rFA at the corona radiata was significantly correlated with poorer motor outcome at admission, after 1u200amonth and after 3u200amonths. Discussion: Clinical motor outcome of ICH within 2u200aweeks can be identified with a statistically significant decrease in rFA at the corona radiata.

Factor VIII Levels are Associated with Ischemic Stroke, Stroke Subtypes and Neurological Worsening

The role played by hemostasis in the pathogenesis of ischemic stroke is still controversial. In the present study, we looked for a possible association of ischemic stroke with the high clotting activity of factor VIII (FVIII). The study population consisted of 116 patients with acute ischemic stroke who had been admitted between September 2013 and September 2014 to the Department of Neurology, Chiayi Chang Gung Memorial Hospital, and 76 control subjects with no history of stroke. FVIII levels were higher in stroke patients as compared to controls (127.5 ± 52.5 vs. 108.4 ± 49.0 IU/dL; P = 0.012). In a univariate risk analysis, FVIII at levels above 150 IU/dL was associated with an odds ratio (OR) for ischemic stroke of up to 2.55 (95% CI, 1.20-5.42, P = 0.013). In a multivariate analysis using a logistic regression model including age, hypertension, low density lipoprotein cholesterol level, estimated glomerular filtration rate, and high FVIII (< 150 IU/dL), high FVIII was still found to significantly add to the risk of ischemic stroke (OR = 3.26 with 95% CI, 1.38-7.68, P = 0.007). As for the stroke subtypes, mean FVIII level was significantly higher in patients with cardioembolic stroke than patients with noncardioembolic stroke (156.0 ± 51.5 IU/dL vs. 124.3 ± 51.9 IU/dL). High levels of FVIII were also associated significantly with neurological worsening (OR = 3.66 with 95% CI, 1.24-10.82, P = 0.019). A high plasma level of FVIII is a prevalent and independent risk factor for ischemic stroke and neurological worsening after acute stroke.

Folic Acid in Stroke Prevention in Countries without Mandatory Folic Acid Food Fortification: A Meta-Analysis of Randomized Controlled Trials

Background and Purpose Additional folic acid (FA) treatment appears to have a neutral effect on reducing vascular risk in countries that mandate FA fortification of food (e.g., USA and Canada). However, it is uncertain whether FA therapy reduces stroke risk in countries without FA food fortification. The purpose of this study was to comprehensively evaluate the efficacy of FA therapy on stroke prevention in countries without FA food fortification. Methods PubMed, EMBASE, and clinicaltrials.gov from January 1966 to August 2016 were searched to identify relevant studies. Relative risk (RR) with 95% confidence interval (CI) was used as a measure of the association between FA supplementation and risk of stroke, after pooling data across trials in a random-effects model. Results The search identified 13 randomized controlled trials (RCTs) involving treatment with FA that had enrolled 65,812 participants, all of which stroke was reported as an outcome measure. After all 13 RCTs were pooled, FA therapy versus control was associated with a lower risk of any future stroke (RR, 0.85; 95% CI, 0.77 to 0.95). FA alone or combination of FA and minimal cyanocobalamin (≤0.05 mg/day) was associated with a lower risk of future stroke (RR, 0.75; 95% CI, 0.66 to 0.86) whereas combination of FA and cyanocobalamin (≥0.4 mg/day) was not associated with a lower risk of future stroke (RR, 0.95; 95% CI, 0.86 to 1.05). Conclusions FA supplement reduced stroke in countries without mandatory FA food fortification. The benefit was found mostly in patients receiving FA alone or combination of FA and minimal cyanocobalamin.

Timing of Symptomatic Infarct Swelling Following Intravenous Thrombolysis in Acute Middle Cerebral Artery Infarction A Case–Control Study

Background: The risk of symptomatic infarct swelling has been reported to be higher in patients treated with recombinant tissue plasminogen activator (rt-PA). The aim of this study was to evaluate the timing of symptomatic infarct swelling after rt-PA treatment. Methods: We retrospectively analyzed 14 868 patients with acute ischemic stroke from a stroke registry databank. We recruited patients with massive middle cerebral artery (MCA) infarction and symptomatic infarct swelling and excluded those with parenchymal or symptomatic hemorrhage. Multiple linear regression and multivariate logistic regression analyses were used to estimate the impact of rt-PA on the timing of symptomatic infarct swelling. Results: A total of 23 patients with rt-PA treatment and 117 patients without rt-PA treatment were included. The rt-PA treatment group had a lower rate of coronary artery disease (8.7% vs 32.5%; P = .023), lower severity of baseline National Institutes of Health Stroke Scale score (19 vs 23; P = .014), shorter duration of infarct swelling (27.6 vs 45.4 hours; P < .001), and higher rate of hemicraniectomy surgery (65.2% vs 28.2%; P =.001) than those without rt-PA treatment. After adjusting for variables in multiple linear regression analysis, rt-PA treatment and an elevated C-reactive protein level were associated with early symptomatic infarct swelling (P = .014 and P = .041, respectively). The rt-PA treatment was an independent factor related to early symptomatic infarct swelling within 36 hours (P = .005; odds ratio [OR]: 5.3; confidence interval [CI]: 1.65-17.0) or 48 hours (P = .009; OR: 16.4; CI: 2.00-134). Conclusion: Intravenous rt-PA treatment may hasten the onset of cerebral edema and subsequent cerebral herniation in large MCA territory infarction.

Low Baseline Urine Creatinine Excretion Rate Predicts Poor Outcomes among Critically Ill Acute Stroke Patients

Urinary creatinine excretion rate (CER) is an established marker of muscle mass. Low CER has been linked to poor coronary artery disease outcomes, but a link between CER and acute stroke prognosis has not been previously explored. We prospectively collected data from patients with acute stroke (ischemic or hemorrhagic) within 24 hours from symptom onset in a Neurological and Neurosurgery Intensive Care Unit in Taiwan. Baseline CER (mg/d) was calculated by urine creatinine concentration in morning spot urine multiplies 24-hour urine volume on the second day of admission. Patients were divided into 3 tertiles with highest, middle, and lowest CER. Primary endpoint was poor outcome defined as modified Rankin Scale 3-6 at 6 months. Among 156 critically ill acute stroke patients meeting study entry criteria, average age was 67.9 years, and 83 (53.2%) patients had ischemic stroke. Patients with lowest CER (vs. highest CER) had a high risk of poor outcome at 6-month after adjustment (odds ratio 4.96, 95% confidence interval 1.22 to 20.15, p value = 0.025). In conclusion, low baseline CER, a marker of muscle mass, was independently associated with poor 6-month outcome among critically ill acute stroke patients. We speculate that preservation of muscle mass through exercise or protein-energy supplement might be helpful for improving prognosis in severe stroke patients.

Magnetic Resonance Perfusion Imaging Provides a Significant Tool for the Identification of Cardioembolic Stroke

Despite advances in imaging techniques and detailed examinations to determine the etiology of a stroke, the cause still remains undetermined in about one fourth of all ischemic strokes. The aim of this prospective study was to determine whether perfusion magnetic resonance imaging (MRI) can differentiate cardioembolic stroke from large artery atherosclerosis (LAA). We recruited 17 cardioembolic stroke and 22 LAA stroke patients, who were classified according to the Trial of Org 10172 in Acute Stroke Treatment and underwent perfusion MRI within 24 hours after the onset of stroke. The patients with cardioembolic stroke had more severe initial stroke severity and larger volumes of initial and final infarct compared to those with LAA stroke. Receiver operating characteristic curve analysis showed that the ratio of time to maximum of the residual curve (Tmax) volume for a 2-, 3-, 4- or 5-s lag over Tmax volume for a 8s lag all had excellent area under the curve values (> 0.9) to predict cardioembolic stroke. After adjusting for initial National Institute of Health Stroke Scale scores, a threshold of 3.73 for (Tmax > 4s volume)/(Tmax > 8s volume) had the highest odds ratio to predict cardioembolic stroke (p=0.012; odds ratio: 58.5; 95% confident interval: 2.5-1391.1), with 87.5% sensitivity and 94.4% specificity. In conclusion, perfusion MRI could be a reliable tool to identify cardioembolic stroke with its lower collateral. This is important as it could be used to reveal the exact mechanism and provide supportive evidence to classify a stroke.

Radiological Features and Post-Operative Drainage Amount Independently Predict Recurrence of Chronic Subdural Hematoma after Burr-holeCraniostomy

Background: Chronic subdural hematoma (CSDH) is a common neurologic disease in elderly. It is not always a benign condition because high recurrence rate had been reported. Independent risk factors for CSDH recurrence, especially the surgical and post-operative factors, had not been sufficiently investigated. nMethods: We retrospectively collected and analyzed data for 125 CSDH patients treated by burr-hole craniostomy in a regional hospital in Taiwan. nResults: Of these CSDH patients, the mean age was 70.2 ± 13.2 years and 96 (76.8%) were males. The CSDH recurrence rate after burr-hole craniostomy was 8.8% in our hospital. The recurrence group had thicker hematoma (24 mm vs. 18.5mm, P=0.024) and more often had laminar type CSDH (27.3% vs. 6.1%, P=0.044) than the non-recurrence group. Multivariate analysis found that thicker hematoma (P=0.033; OR=1.121; 95% CI 1.01-1.25), laminar type CSDH (P=0.010; OR=13.461; 95% CI 1.87-97.14) and larger total post-operative drainage amount (P=0.021; OR=1.002; 95% CI 1.000−1.004) were independently associated with recurrence of CSDH after burr-hole craniostomy. We didn’t find an association between burr hole numbers and recurrence rate. nConclusion: We found thicker hematoma,laminar type CSDH and larger post-operative drainage amounts independently predict recurrence of CSDH after burr-hole craniostomy. The patients with these risk factors may need closer surveillance post-operatively. Further studies are needed for surgical method modification to achieve lower recurrence rate.