Statin treatment in stroke patient with low-density lipoprotein cholesterol levels below 70 mg/dL.

BACKGROUND AND PURPOSE: The effectiveness of hyperlipidemia treatment in strokes secondary prevention has been established. However, whether pretreatment with statins could confer protective effects when a patient's baseline low-density lipoprotein cholesterol (LDL-C) level is <70 mg/dL remains uncertain. Additionally, the ability of statin treatment to reduce poststroke complications, mortality, and recurrence in this patient group is unclear. METHODS AND RESULTS: In this retrospective observational study, we enrolled patients who had experienced an ischemic stroke with LDL-C levels <70 mg/dL. We analyzed the association of statin use with baseline characteristics, stroke severity, in-hospital complications, mortality rates, stroke recurrence rate, and mortality rate. Patients who used and patients who did not use statins were similar in terms of age and sex. Patients using statins had higher rates of diabetes mellitus, hypertension, prior stroke, and coronary artery disease but a lower incidence of atrial fibrillation. Stroke severity was less pronounced in those using statins. We also evaluated the relationship between in-hospital statin use and complications. We noted that in-hospital statin use was associated with lower rates of infection, hemorrhagic transformation, gastrointestinal hemorrhage, and mortality, as well as higher rates of positive functional outcomes. The 1-year recurrence rate was similar in both groups. CONCLUSIONS: Statin use is associated with milder strokes and improved poststroke outcomes, even in patients with well-controlled LDL levels. Neurologists may consider prescribing statins for patients with ischemic stroke who do not overt hyperlipidemia. Further research into potential underlying mechanisms is warranted.

Effects of cancer on stroke recurrence and mortality: A single-center retrospective cohort study.

Background: Whether patients with stroke and cancer have specific characteristics remains controversial. In addition, research regarding the effects of individual cancer types on stroke outcomes remains scarce. This study investigated the mortality and stroke recurrence rates in patients with stroke and concomitant cancer and evaluated outcome predictors. Methods: This study retrospectively enrolled 2610 patients in the Taipei Veterans General Hospital Stroke Registry registered from January 2019 to December 2020. A total of 1868 patients were included after excluding those without acute ischemic stroke or hospitalization. The patients were then categorized into the following diagnostic groups: cancer-associated stroke (CAS), stroke and inactive cancer, and stroke without cancer. The discharge mortality rate, 1-year mortality rate, and 1-year stroke recurrence rate were compared. Multiple clinical characteristics and comorbidities-age, sex, stroke severity, coagulopathy, common vascular risk factors, and acute stroke treatment-were also assessed. Results: A total of 302 (16.2%) patients had concomitant cancer; 39 (2.1%) patients were classified as having CAS and 263 (14.1%) as having stroke with inactive cancer. The baseline characteristics, stroke severity, and type of acute reperfusion therapy were similar among the three groups. However, the stroke recurrence and mortality rates were much higher in the patients with CAS in both short-term and long-term follow-up. The 30-day and 1-year mortality rates for the CAS, inactive cancer, and no cancer groups were 17.9%, 12.5%, and 4.7%, (p < 0.001) and 51.3%, 33.8%, and 12.4%, (p < 0.001) respectively. Conclusion: Patients with stroke and active cancer had similar stroke severity. However, the 1-year mortality and stroke recurrence rates were higher in these patients than in patients with inactive cancer or the control group.

The 2020 Taiwan Stroke Society guidelines for blood pressure control at the acute stage of ischemic stroke.

The 2020 Taiwan Stroke Society (TSS) guidelines for blood pressure (BP) control related to ischemic stroke update the 2015 TSS BP guidelines. The early management of acute ischemic stroke has evolved rapidly in the previous two decades. Since the publication of the previous version of the TSS BP guidelines, many studies have addressed BP management in ischemic stroke. Particularly, several successful endovascular thrombectomy (EVT) trials published in 2015 led to a new era of acute treatment for ischemic stroke. With the ever-increasing use of EVT, evidence-based guidelines for ideal BP management during and after EVT are urgently needed. Consequently, the 2020 guidelines are updating and providing recommendations on BP control for the treatment and prevention of ischemic stroke based on new evidence. The present study encompasses the most important chapter of the 2020 Taiwan BP guidelines: BP control at the acute stage of ischemic stroke. We incorporated the most updated evidence regarding BP control at the acute stage of ischemic stroke in patients receiving or not receiving acute reperfusion therapy and provided specific recommendations for different treatment subgroups accordingly.

2021 Taiwan Stroke Society Guidelines of blood pressure control for ischemic stroke prevention.

BACKGROUND: Since the publication of the 2015 Taiwan Stroke Society Blood Pressure for Treatment and Prevention of Stroke Guideline (2015 TSS BP Guideline), several new clinical studies have addressed whether a stricter blood pressure (BP) target would be effective for stroke prevention. METHODS: TSS guideline consensus group provides recommendations on BP targets for stroke prevention based on updated evidences. RESULTS: The present guideline covers five topics: (1) diagnosis of hypertension; (2) BP control and primary prevention of ischemic stroke; (3) BP control and secondary prevention of ischemic stroke; (4) BP control and secondary prevention of large artery atherosclerosis ischemic stroke; and (5) BP control and secondary prevention of small vessel occlusion ischemic stroke. CONCLUSION: The BP target for most stroke patients with hypertension is <130/80 mm Hg.

Urgent Demand of Network Access for Acute Ischemic Stroke Management in Taiwan.

Time is the major determinant in successful reperfusion therapy of acute ischemic stroke. The evolving diagnostic tools and treatment of acute stroke has made a great progress in the past 2 decades and is remolding current management practices. It demands a timely neurologic evaluation and a neuroimaging study to determine if stroke patients are appropriate candidates for reperfusion demands. Therefore, it is critical for the setting of stroke center accreditation levels and capabilities so that timely and appropriate treatment is initiated for the eligible stroke patients. Optimal acute ischemic stroke treatment requires all levels of stroke center network operating efficiently. In the future, Taiwan should revise the criteria of stroke center accreditation and set up the efficient acute stroke treatment network as soon as possible. Keywords: stroke, reperfusion, intra-arterial thrombectomy, intravenous recombinant tissue plasminogen activator.

Etiology and risk factors of intracranial hemorrhage and ischemic stroke in young adults.

BACKGROUND: Young stroke incidence has increased worldwide with lifestyle changes. Etiology and risk factors for both ischemic and hemorrhagic stroke in young Asians remain underexplored. METHODS: We retrospectively reviewed consecutive acute stroke patients aged 16-45 years admitted to the Taipei Veterans General Hospital between 2009 and 2019 to analyze etiologic subtypes, risk factors, and serial modified Rankin Scale scores for 1 year and compare the age groups of 16-30 and 31-45 years. RESULTS: Among 670 young Taiwanese patients (mean age at onset 37.5 ± 7.0 years; male 65.1%), there were 366 nontraumatic spontaneous hemorrhagic stroke (including 259 intracerebral hemorrhage [ICH] and 107 subarachnoid hemorrhage, SAH), 292 ischemic stroke and 12 cerebral venous thromboses. Notably, ICH was more prevalent in patients aged 16-30 than in those aged 31-45 (54.8% vs 36.8%). Specifically, structural vasculopathy (e.g., arteriovenous malformation, cavernoma) was the most common etiologic subtype in patients aged 16-30 (p < 0.001), whereas hypertensive ICH was the most common subtype in patients aged 31-45 (p < 0.001). On the other hand, the top ischemic subtype for both age groups was other determined diseases (e.g., arterial dissection, autoimmune diseases, moyamoya disease, etc.) rather than large artery atherosclerosis. Hyperlipidemia, diabetes, and cigarette smoking were more common risk factors for infarction than ICH. Familial stroke patients whose first- or second-degree relatives had a stroke by age 80 (n = 104, 15.5%) had more infarctions than those without a familial stroke history. In multivariate analyses, initial stroke severity, and infarction type were important predictors of favorable outcomes after 3 months. At the 1-year follow-up, patients with ICH and SAH had worse functional outcomes and survival rates than those with infarction. CONCLUSION: An aggressive approach to elucidate the etiology of stroke is indicated because structural vasculopathy-induced ICH and other determined infarction are distinctively prevalent in young adults, particularly those aged 16-30.

Quantitative CT angiography predicts large artery occlusion types and successful thrombectomy in acute ischemic stroke.

BACKGROUND: Clinical and radiological outcomes of endovascular thrombectomy (EVT) are related to etiologies of large vessel occlusion (LVO) in acute stroke. However, preprocedural computed tomography angiography (CTA) or CT perfusion imaging can hardly distinguish embolic occlusion from atherosclerotic occlusion. We hypothesized that quantitative multiphase CTA (mCTA) of LVO may predict occlusion types and thrombectomy outcome. METHODS: We retrospectively evaluated the consecutive stroke patients who had undergone mCTA and EVT <6 hours of onset at two independent medical centers. The intra-arterial radiodensities of Hounsfield unit (HU) were measured to examine the HUdistal/proximal ratio using receiver operating characteristic curve analysis. The derived cut-off value was re-examined in an independent cohort. RESULTS: In the derivation cohort (n = 102), 81 patients (79.4%) were embolic occlusion without severe residual intracranial atherosclerotic stenosis (ICAS[-]) and 21 patients were atherosclerosis-related occlusion (ICAS[+]) based on digital subtraction angiography (DSA). The optimal cut-off to predict embolic occlusion was HU ratio <0.6 measured at 2 mm from the occlusion site (maximum area under the curve = 0.87; sensitivity 96%; specificity 81%). This cut-off also independently predicted successful recanalization using stent-retrievers and/or contact aspiration (modified Treatment in Cerebral Ischemia score ≥2b; p = 0.002) after adjusting for age, atrial fibrillation, and collateral circulation score, but not predicted favorable outcome at 3 months post stroke. Importantly, in the validation cohort (n = 95, 80% embolic occlusion), this HU ratio cut-off similarly predicted occlusion types and recanalization outcome, respectively. CONCLUSION: The mCTA-based quantitative radiodensities of acute LVO provides preprocedural predictive values of DSA-determined occlusion types and thrombectomy outcomes.

Premature Atrial Contractions and Their Association with Stroke Features and Outcome.

BACKGROUND: Frequent premature atrial contractions (PACs) are associated with atrial fibrillation, stroke, and mortality. However, the cut-off value for PAC counts that could identify patients with different stroke features is unclear, and the association of PACs to outcome is not determined. METHODS: The study retrospectively included patients with acute ischemic stroke who had underwent both a 24 h Holter recording and a brain MRI in Taipei Veterans General Hospital from January 2015 to May 2016. Patients were categorized into four groups according to their PAC frequencies on 24 h Holter recording. We compared the clinical severity, neuroimage features, stroke subtypes, and functional outcome among the four groups of patients. RESULTS: Among the 278 patients, the lower, middle, and upper quartiles of the PAC counts were 23, 74, and 459.5, respectively. In contrast to the 1st quartile of patients, the 3rd (PAC 75-459/24 h) and the 4th (PAC ≥460/24 h) quartiles of patients had higher NIH Stroke Scale (NIHSS) at admission (p = 0.014 and p = 0.002, respectively). The frequencies of cryptogenic stroke were not different among the 4 quartiles of the patients, but cryptogenic stroke patients with ≥ 75PACs/24hours had higher stroke severity compared to those with PACs < 75counts/24 h (NIHSS 9.1 vs. 5.2, p = 0.043). There was an increased trend in infarcts of multiple vascular territories and in mortality at 1 year among the four groups of patients with increased PAC frequency (p = 0.045 and p = 0.002, respectively). The 4th PAC quartile was associated with poor functional outcome (modified Rankin Scale ≥ 4) at 3 months in univariate analysis (OR: 5.66, CI: 2.69-11.91, p < 0.001), but was not an independent predictor after controlling for initial stroke severity. CONCLUSIONS: PACs ≥ 75 counts/24 h was associated with higher clinical severity in patients with acute ischemic stroke.

Better endovascular mechanical thrombectomy outcome in atrial fibrillation patients with acute ischemic stroke: A single-center experience.

BACKGROUND: Endovascular thrombectomy (EVT) has become the standard treatment for acute ischemic stroke with large vessel occlusion. Atrial fibrillation (AF) is one of the major causes. However, the impact of AF on the treatment has not yet been clearly discussed. This study is to evaluate the influence of AF on the outcomes of EVT in patients with acute ischemic stroke. METHODS: Data from our Stroke Registry Database from April 2015 to July 2018 were reviewed. Technical efficacy, functional, and safety outcomes were reported and compared between patients with and without AF. A multivariate logistic regression model was performed to identify the predictors of the good functional outcome. RESULTS: We reviewed 83 eligible patients receiving EVT. Patients (51.8%) were eventually found to have AF. The substantial reperfusion rate (modified thrombolysis in cerebral infarction 2b-3) was 72.1% and 55.0% in patients with and without AF, respectively, inclusive of a learning curve (p = 0.12). The good functional outcome (90-day modified Rankin scale: 0 to 2) rate was 55.8% and 17.5% in patients with and without AF, respectively (p < 0.01). A multivariable logistic regression analysis showed that age <70 years, the substantial reperfusion, and the presence of AF were three significant predictors for a good functional outcome. CONCLUSION: Our study showed that patients with AF responded significantly better to EVT than those without AF did. Intracranial atherosclerotic diseases in patients without AF which were especially refractory to EVT may contribute to the difference of the functional outcomes between the two groups.

RGS5 rs4657251 polymorphism is associated with small vessel occlusion stroke in Taiwan Han Chinese.

BACKGROUND: The regulator of G-protein signaling protein 5 (RGS5) has been demonstrated to play a role in regulating blood pressure and cardiovascular function. Studies have shown that RGS5 polymorphisms exhibit susceptibility to hypertension. However, no study has yet been performed among stroke patients. METHODS: To evaluate whether RGS5 rs4657251 is a susceptibility gene for stroke, we performed a case-control association study involving 714 large-artery atherosclerosis (LAA) patients, 383 small vessel occlusion (SVO) patients, 401 hypertensive intracranial hemorrhages (HICH), and 626 controls. The RGS5 rs4657251 polymorphism was analyzed through polymerase chain reaction. RESULTS: The TC genotype was significantly higher in the SVO group compared with that in the control group (odds ratio [OR] = 1.34, 95% confidence interval [CI] = 1.02-1.76, p = 0.035). In addition, the dominant phenotype (TC + CC vs TT) was also significantly different between the SVO and the control groups (OR = 1.31, 95% CI = 1.01-1.70, p = 0.046). However, no association was found between RGS5 rs4657251 and LAA an HICH. After adjustment with gender, diabetes, smoking, cholesterol and low-density lipoprotein levels, RGS5 rs4657251 polymorphism remained an independent risk factor for SVO (OR = 1.49; 95% CI = 1.12-1.98) but not for LAA or HICH. CONCLUSION: Our findings, obtained among Taiwan Han Chinese subjects, provide the first evidence that RGS5 rs4657251 polymorphism is an independent risk factor for SVO.

Association of apolipoprotein A1 and A5 polymorphisms with stroke subtypes in Han Chinese people in Taiwan.

BACKGROUND AND PURPOSES: Stroke is a leading cause of death and serious disability worldwide. Now, evidences indicate that dyslipidemia may play an important role in stroke. APOA1 and APOA5 involve in lipid metabolism. In this study, we investigated the association of APOA1 rs670 and APOA5 rs662799 with different stroke subtypes in the Han Chinese population of Taiwan. METHODS: A total of 1751 participants, including 459 control subjects, 606 large artery atherosclerosis (LAA), 339 small vessel occlusion (SVO), and 347 hypertensive intracranial hemorrhage (HICH), were enrolled. The presence of rs670 and rs662799 was analyzed through polymerase chain react ion and matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry. RESULTS: Notably, the frequency of the rs662799 C allele was significantly lower in the SVO patients than in the controls (24.36% vs. 29.74%, P = 0.024). The frequencies of heterozygote TC [odd ratio (OR) = 0.732, 95% confidence interval (CI) = 0.544-0.984, P = 0.038] and TC + CC (OR = 0.719, 95% CI = 0.542-0.953, P = 0.022) genotypes were significantly lower in the SVO patients than in the controls. In addition, triglyceride levels in individuals carrying the rs662799 TC + CC genotype were significantly higher than in those carrying the TT genotype, especially in older age, female, and body mass index (BMI) ≥ 25 groups. On the contrary, the low-density lipoprotein-cholesterol (LDL-C) was significantly lower in rs662799 TC + CC genotype than TT genotype. The BMI was significantly lower in subjects with rs662799 TC + CC genotype than those with TT genotype, especially in older age and female. High-density lipoprotein-cholesterol (HDL-C) levels were higher in individuals carrying the rs670 GG genotype than in those carrying the AG + AA genotype, especially in BMI < 25 group. Logistic regression analysis showed that the rs662799 C allele (TC + CC) was an independent protective factor for SVO after adjustment for conventional risk factors (OR = 0.709, 95% CI = 0.526-0.956; P = 0.024). CONCLUSION: GG genotype of rs670 is correlated with high serum HDL-C levels, whereas TC + CC genotype of rs662799 is associated with high serum triglyceride and low LDL and BMI levels. In addition, the rs662799 C allele (TC + CC) is an independent protective factor for SVO in the Han Chinese population in Taiwan.

Apolipoprotein A1 rs5070 A/G polymorphism with stroke subtypes in Taiwan.

BACKGROUND: Apolipoprotein A1 (ApoA1) is a structural protein of high-density lipoprotein cholesterol; ApoA1 is involved in lipid and cholesterol metabolism. This study evaluated the association of ApoA1 polymorphism (rs5070) with different stroke subtypes in Taiwanese individuals. METHODS: A total of 2139 cases, including 614 controls and 708 large artery atherosclerosis (LAA), 377 small-vessel occlusion, and 440 hypertensive intracranial hemorrhage cases, were enrolled in this study. ApoA1 polymorphism was genotyped through polymerase chain reaction amplification and then subjected to mass-assisted laser desorption ionization time-of-flight mass spectrometry using a Bruker SNP genotyping system in the National Center for Genome Medicine (Academia Sinica, Taipei, Taiwan; http://ncgm.sinica.edu.tw/). RESULTS: The frequency of ApoA1 rs5070 dominant genotype (AA vs. AG+GG) was not significantly different among LAA, small-vessel occlusion, and hypertensive intracranial hemorrhage groups compared with that of the control group. Compared with diabetic patients with the AA allele, those with the AG+GG allele of ApoA1 rs5070 polymorphism showed a 1.58-fold likelihood of developing LAA (odds ratio=1.58; 95% confidence interval=1.00-2.42; p=0.046), but not small-vessel occlusion or hypertensive intracranial hemorrhage. In male diabetic patients, the odds ratio increased to 1.90-fold. CONCLUSION: Our findings suggested that genetic polymorphisms of ApoA1 rs5070 A/G may play a role in the susceptibility to LAA among male diabetic patients.

The assessment of anticoagulant activity to predict bleeding outcome in atrial fibrillation patients receiving dabigatran etexilate.

Special circumstances may require the measurement of the anticoagulant effect of dabigatran etexilate. No data currently link any given coagulation test to bleeding outcomes in patients receiving dabigatran etexilate for atrial fibrillation. Nonvalvular atrial fibrillation patients receiving dabigatran etexilate of 110 mg (DE110) or 150 mg (DE150) were consecutively enrolled. The hemoclot thrombin inhibitor (HTI) assay, prothrombin time, and activated partial thromboplastin time (APTT) measurements were correlated with bleeding events during a prospective follow-up. There were 17 bleeding events (8.2%) in 208 patients (74.7 ±â€Š10.3 years old, 67.9% male, median follow-up: 364 days), whereas 15 patients with bleeding events used DE110. Compared with DE110, the patients receiving DE150 were younger and more often male and had lower HAS-BLED and CHA2DS2VASc scores and better renal function. Patients' HTI levels were very variable (DE110, 10-90th percentile: 20.5-223.9 ng/ml). A receiver-operator characteristic curve gave a median cutoff HTI level of 117.7 ng/ml to predict bleeding events (C-statistics: 0.65; P = 0.036), but no cutoff could be determined for prothrombin time or APTT. Based on the Kaplan-Meier analysis, a dabigatran etexilate level greater than 117.7 ng/ml was associated with a higher bleeding rate (15.4% vs. 4.9%, P = 0.01). After multivariate Cox regression analysis, HTI levels, history of stroke, and male sex were independent risk factors for bleeding events. Dabigatran etexilate-HTI levels were independently associated with bleeding in patients receiving routine clinical care. Blood sampling at multiple time points might be needed to increase reliability because of high variation of dabigatran etexilate-HTI levels.

Identification and management of noncompliance in atrial fibrillation patients receiving dabigatran: the role of a drug monitor.

BACKGROUND: Noncompliant patients might be at risk of thromboembolism because of the short half-life and rapid offset of dabigatran etexilate. The assessment and management of dabigatran noncompliance should be optimized. METHODS AND RESULTS: A total of 150 nonvalvular atrial fibrillation patients receiving dabigatran were prospectively enrolled and followed for drug compliance and persistence. Noncompliance was identified by questionnaires and interviews. The hemoclot thrombin inhibitor (HTI) assay was used for monitoring the plasma dabigatran levels. Sixteen patients were noncompliant (10.7%). None of the clinical characteristics were significantly relevant to noncompliance after multivariate analysis. The dabigatran plasma level based on HTI was the only independent predictor of noncompliance (odds ratio: 0.97 per ng/mL, P = 0.003). The prothrombin time (PT), international normalized ratio of PT (INR [PT]), and activated partial thromboplastin time did not differ between compliant and noncompliant patients. During the follow-up, the persistent prescription of dabigatran was noted in 75% of noncompliant patients without improvement in compliance. The drug discontinuation rate was higher in the noncompliant than compliant patients (6.7% vs. 25%, P = 0.035). None of the patients in either group received warfarin after discontinuing dabigatran. CONCLUSIONS: The assessment and management of dabigatran noncompliance is generally ignored in clinical practice. The measurement of dabigatran plasma levels by HTI could be a reliable and simple method to identify noncompliant patients.

Impact of carotid stenting in dizzy patients with carotid stenosis.

BACKGROUND: Little is known about the impact of severe carotid stenosis on health-related quality of life (HRQoL). The aim of this study was to assess the effects of carotid stenting (CAS) on HRQoL in dizzy patients with carotid stenosis. METHODS: Patients with symptomatic (≥60%) or asymptomatic (≥80%) severe carotid stenosis and who complained of dizziness and received CAS were recruited. Two HRQoL questionnaires-a generic survey, the 36-item Short-Form Health Survey and a disease-specific instrument, the Dizziness Handicap Inventory-served as outcome measures. Patients were followed 1 week prior to CAS and 6 months postprocedurally. RESULTS: CAS was performed in 178 consecutive patients, 61 of whom complained of dizziness. Forty-one patients (67.2%, 34 male; mean age, 73.3 ± 10.5 years; range, 47-87 years) completed the study. Twenty asymptomatic volunteers (17 male; mean age, 70.3 ± 9.3 years; range, 54-84 years) served as normal controls. Compared to controls, patients tallied lower scores in the overall total and three subscales (physical, functional, and emotional) of the Dizziness Handicap Inventory (p < 0.01). Similar findings were noted in seven out of eight domains of the 36-item Short-Form Health Survey score. After 6 months, CAS resulted in significantly improved HRQoL (role physical, bodily pain, general health, social function, and role emotional) in these patients. CONCLUSION: CAS resulted in improved HRQoL in patients with severe carotid stenosis who experienced dizziness.

Complexity of human postural control in subjects with unilateral peripheral vestibular hypofunction.

Complexity is a new measure for identifying the adaptability of a complex system to meet possible challenges. For a center of pressure (COP) time series, the complexity measure represents the stability of postural control. In this study, multiscale entropy (MSE) was used to evaluate the complexity of COP time series in six test conditions of sensory organization test (SOT). Complexity index (CI) is defined as the summation of entropies with coarse-graining scales 1-20 by MSE. A total of 51 subjects belonging to 3 groups - healthy-young, healthy-elderly and dizzy - were recruited in this study. The COP signals in both anteroposterior (AP) and mediolateral (ML) directions were analyzed respectively. According to our results, the CI of AP-direction COP time series is significantly correlated to the equilibrium score, which represents the stability of postural control in SOT. The AP-direction sway is significant larger than the ML-direction sway, particularly in the test conditions with sway-surface. In additions, the CI of AP-direction COP for the healthy-elderly and dizzy groups are significantly lower than those for the healthy young group in the test conditions 1-4. The CI of ML-direction COP for the healthy-elderly group is significantly lower than those for the healthy-young and dizzy groups under test conditions 3 and 6. These results show that the complexity loss is a common status of AP-direction COP time series for both healthy-elderly and dizzy groups, and the complexity of ML-direction COP time series for subjects with unilateral vestibular dysfunction is higher than that for the healthy-elderly group specifically under test conditions 3 and 6.

Nonlinear analysis of sensory organization test for subjects with unilateral vestibular dysfunction.

Vestibular disorder is the cause of approximately 50% of dizziness in older people. The vestibular system is a critical postural control mechanism, and posturography analysis is helpful for diagnosing vestibular disorder. In clinical practice, the sensory organization test (SOT) is used to quantify postural control in an upright stance under different test conditions. However, both aging and vestibular disorder cause declines of postural control mechanisms. The aim of this study was to enhance the performance of the SOT using a nonlinear algorithm of empirical mode decomposition (EMD) and to verify the differences of effects caused by aging and/or illnesses benefits to clinical diagnosis. A total of 51 subjects belonging to 3 groups--healthy-young, healthy-elderly and dizzy--were recruited for this study. New dynamic parameters of the SOT were derived from the center of pressure (COP) signals. EMD served as an adaptive filter bank to derive the low- and high-frequency components of the COP. The effects on four ratios of sensory analysis caused by aging and vestibular disorder can be investigated for the specific frequency bands. According to our findings, new SOT parameters derived from the component with the specific frequency band more sensitively reflect the functional condition of vestibular dysfunction. Furthermore, both aging and vestibular dysfunction caused an increase in magnitude for the low-frequency component of the AP-direction COP time series. In summary, the low-frequency fluctuation reflects the stability of postural control, while the high-frequency fluctuation is sensitive to the functional condition of the sensory system. EMD successfully improved the accuracy of SOT measurements in this investigation.

Exposure to benzidine caused apoptosis and malformation of telencephalon region in zebrafish.

Exposure to benzidine has been known to induce human cancers, particularly bladder carcinomas. In this study, the zebrafish model was used to investigate the developmental toxicity of benzidine. Embryos at 6 h postfertilization (hpf) that were exposed to benzidine exhibited embryonic death in a dose- and time-dependent manner. Benzidine induced malformations in zebrafish, such as small brain development, shorter axes, and a slight pericardial edema. High concentrations (50, 100, and 200 µM) of benzidine triggered widespread apoptosis in the brain and dorsal neurons, as evidenced by acridine orange and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays. Real-time polymerase chain reaction analysis also showed that benzidine treatment affected p53, bax, and noxa expression. Decreases in specific brain markers, such as emx1 in the telencephalon, ngn1 in differentiated neurons, and otx2 in the midbrain, were observed in benzidine-treated embryos at 24 hpf. Conversely, no overt changes to pax2.1 expression in the midbrain-hindbrain boundary were found. Moreover, the use of Tg(HuC:GFP) zebrafish showed that benzidine caused a malformation of the telencephalon region. Our findings show that benzidine exposure triggers widespread apoptosis in the zebrafish brain and dorsal neurons, resulting in the development of an abnormal telencephalon.