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.

Diagnosis and Treatment for embolic stroke of undetermined source: Consensus statement from the Taiwan stroke society and Taiwan society of cardiology.

Cryptogenic stroke comprises about one-quarter of ischemic strokes with high recurrence rate; however, studies specifically investigating the features and treatment of this stroke subtype are rare. The concept of 'embolic stroke of undetermined source' (ESUS) may facilitate the development of a standardized approach to diagnose cryptogenic stroke and improve clinical trials. Since recent large randomized control trials failed to demonstrate a reduction in stroke recurrence with anticoagulants, anti-platelet agents remain the first-line treatment for ESUS patients. Nevertheless, patients with high risk of stroke recurrence (e.g., those with repeated embolic infarcts despite aspirin treatment) require a more extensive survey of stroke etiology, including cardiac imaging and prolonged cardiac rhythm monitoring. Anticoagulant treatments may still benefit some subgroups of high-risk ESUS patients, such as those with multiple infarcts at different arterial territories without aortic atheroma, the elderly, or patients with high CHA2D2-VASc or HOVAC scores, atrial cardiopathy or patent foramen ovale. Several important ESUS clinical trials are ongoing, and the results are anticipated. With rapid progress in our understanding of ESUS pathophysiology, new subcategorizations of ESUS and assignment of optimal treatments for each ESUS subgroup are expected in the near future.

Association of Serum Uric Acid with Cardiovascular Disease in Taiwanese Patients with Primary Hypertension.

BACKGROUND: Hyperuricemia is closely linked to hypertension and may be a marker of susceptibility or an intermediate step in the development of metabolic syndrome. However, recently, there have been conflicting conclusions regarding the independent role of uric acid as a risk factor of cardiovascular disease (CVD). The specific role of serum uric acid (SUA) in relation to CVD remains controversial, and there are limited reports utilizing Asian data available on this issue. Therefore, this study investigated the association between SUA and cardiovascular disease in Taiwanese patients with essential hypertension. METHODS: There were 3472 participants from 55-80 years of age (1763 males, 1709 females) from 38 sites across Taiwan in this hospital-based cross-sectional study, covering the period November 2005 to December 2006. The CVD included diagnosed angina pectoris, myocardial infarction, congestive heart failure, and stroke. RESULTS: Hyperuricemia is positively associated with CVD in both sexes when a unified cut-off SUA level of 7 mg/dl was used. However, the odds ratios (ORs) for all CVD were greater in magnitude in hypertensive women than in men when there was co-morbidity of diabetes. The ORs of all CVD in the diabetes subgroup were statistically significantly (p = 0.01 for women, p = 0.07 for men). By multivariate analysis, hyperuricemia did not confer an increased risk of CVD. CONCLUSIONS: Hyperuricemia may be associated with increased risk of CVD, but is not an independent risk factor of CVD in essential hypertensive Taiwanese patients. KEY WORDS: Cardiovascular disease; Hypertension; Hyperuricemia; Uric acid.

Investigating Undiagnosed Fabry Disease in Young Adults with Ischemic Stroke: A Multicenter Cohort Study.

BACKGROUND: The global prevalence of ischemic stroke in young adults is increasing, leading to a significant social impact. Fabry disease is a recognized cause of ischemic stroke in young patients, and although disease-modifying treatments are available, further evidence is needed to confirm their effectiveness in reducing the incidence of ischemic strokes. AIMS: This study aimed to identify undiagnosed Fabry disease in young adult patients with ischemic stroke in a Taiwanese cohort. METHODS: This multicenter, prospective cohort study enrolled patients aged 20 to 55 years who had experienced an ischemic stroke or transient ischemic attack (TIA) within 10 days, from January 1, 2016, to December 31, 2020. Screening for Fabry disease was performed using a dry blood test to measure α-galactosidase activity in male patients and blood globotriaosylsphingosine (lyso-Gb3) levels in female patients. For patients with positive screen results, genetic diagnosis of Fabry disease was pursued through Sanger sequencing of the GLA gene, covering all exons and a segment of intron 4. RESULTS: A total of 977 patients (659 male, 68%) were enrolled from 7 hospitals across Taiwan. Four patients (0.4%, all male) had positive screening results, and 2 patients (0.2%) were genetically diagnosed with Fabry disease. Case 1 had the GLA c.658C>T mutation and experienced ischemic stroke in the bilateral occipital regions. Case 2 had the GLA c.640-801G>A mutation and experienced an ischemic stroke in the left superficial watershed area. CONCLUSIONS: The prevalence of undiagnosed Fabry disease in this cohort of Taiwanese young adults with ischemic stroke or TIA was 0.3% among the young male population. Understanding the prevalence of undiagnosed Fabry disease in young adults with ischemic stroke could help shape future Fabry disease screening policies.

Body composition, C-reactive protein, carotid artery remodeling and subclinical atherosclerosis in a general Taiwanese population.

Obesity, an escalating problem worldwide, increases the risk of serious disease, particularly atherosclerosis. A community-based cross-sectional study was designed to screen for undetected atherosclerosis. High-sensitivity C-reactive protein (hs-CRP), the presence of the metabolic syndrome (MetS), and ultrasound studies to detect fatty liver and measure carotid intimal-medial thickness were performed. A total of 1,005 subjects (595 men and 410 women; mean age of 52.4 ± 11.1 years) were included in the final study cohort. 237 subjects (23.7%) fulfilled National Cholesterol Education Program Adult Treatment Panel ATP-III criteria for MetS. Significant differences between female and male subjects were noted in body mass index (BMI), % body fat mass (Fat%), waist-to-hip ratio, waist circumference, fasting glucose levels, triglyceride levels, fatty liver, and carotid artery changes (P < 0.05). When female subjects were classified by hs-CRP levels, significant differences were reported among the three groups in age, BMI, Fat%, waist-to-hip ratio, waist circumference, blood pressure, fasting glucose, HDL, triglycerides, fatty liver grade and common carotid artery changes (P < 0.05). In this study, high hs-CRP was associated with increased cholesterol and cardiovascular changes supporting the idea that it may be a useful biomarker for detecting early asymptomatic vascular and coronary heart disease resulting from obesity.

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.

Effectiveness of Standard-Dose vs. Low-Dose Alteplase for Acute Ischemic Stroke Within 3-4.5 h.

BACKGROUND: The efficacy and safety of intravenous alteplase administered 3-4.5 h after acute ischemic stroke have been demonstrated. However, whether responses differ between low-dose and standard-dose alteplase during this time window and whether certain subgroups benefit more remain unknown. PATIENTS AND METHODS: The current analysis was based on a multicenter matched-cohort study conducted in Taiwan. The treatment group comprised 378 patients receiving intravenous alteplase 3-4.5 h after stroke onset, and the control group comprised 378 age- and sex-matched patients who did not receive alteplase treatment during the same period. Standard- and low-dose alteplase was administered to patients at the physician's discretion. RESULTS: Overall, patients receiving alteplase exhibited more favorable outcomes than did controls [34.0 vs. 22.7%; odds ratio (OR): 1.75, 95% confidence interval (CI): 1.27-1.42], and the effectiveness was consistent in all subgroups. Although patients in the standard-dose group (n = 182) were younger than those in the low-dose (n = 192) group, the proportions of patients with favorable outcomes (36.3 vs. 31.8%; OR: 1.22, 95% CI: 0.80-1.88) and symptomatic hemorrhage (2.8 vs 4.2%; OR: 0.65, 95% CI: 0.21-2.02) were consistently comparable in a covariate-adjusted model and an age-matched cohort. In the subgroup analysis, patients with cardioembolism, atrial fibrillation, and hypercholesterolemia were more likely to achieve favorable outcomes after receiving standard-dose than low-dose alteplase. CONCLUSION: In the 3-4.5 h time window, the effectiveness and safety of standard-dose and low-dose alteplase may be comparable. A standard dose may be selected for patients with cardioembolism, atrial fibrillation, or hypercholesterolemia.

Leukoencephalopathy after levamisole for the treatment of verrucae.

PURPOSE: Levamisole is an antihelmintic and immunomodulator used as a dewormer and in combination with other forms of chemotherapy to treat colon cancer, melanoma, and head and neck cancer. It has also been used for treating dermatologic disorders such as verrucae. However, its benefits remain controversial and serious side effects such as central nervous system toxicity are unexpected. CASE REPORT: Multifocal leukoencephalopathy developed in a 26-year-old man after levamisole treatment for verrucae. He recovered completely after discontinuation of the offending drug and treatment with steroid and plasmapheresis. CONCLUSION: Clinicians should be aware of this neurotoxicity in order to provide early diagnosis and treatment and thereby improve outcome.

Prevalence and Effect of Cerebral Small Vessel Disease in Stroke Patients With Aspirin Treatment Failure-A Hospital-Based Stroke Secondary Prevention Registry.

Background: Breakthrough strokes during treatment with aspirin, termed clinical aspirin treatment failure (ATF), is common in clinical practice. The burden of cerebral small vessel disease (SVD) is associated with an increased recurrent ischemic stroke risk. However, the association between SVD and ATF remains unclear. This study investigated the prevalence and clinical characteristics of SVD in stroke patients with ATF. Methods: Data from a prospective, and multicenter stroke with ATF registry established in 2018 in Taiwan were used, and 300 patients who developed ischemic stroke concurrent with regular use of aspirin were enrolled. White matter lesions (WMLs) and cerebral microbleeds (CMBs) were identified using the Fazekas scale and Microbleed Anatomical Rating Scale, respectively. Demographic data, cardiovascular comorbidities, and index stroke characteristics of patients with different WML and CMB severities were compared. Logistic regression analyses were performed to explore the factors independently associated with outcomes after ATF. Results: The mean patient age was 69.5 ± 11.8 years, and 70.0% of patients were men. Among all patients, periventricular WML (PVWML), deep WML (DWML), and CMB prevalence was 93.3, 90.0, and 52.5%, respectively. Furthermore, 46.0% of the index strokes were small vessel occlusions. Severe PVWMLs and DWMLs were significantly associated with high CMB burdens. Patients with moderate-to-severe PVWMLs and DWMLs were significantly older and had higher cardiovascular comorbidity prevalence than did patients with no or mild WMLs. Moreover, patients with favorable outcomes exhibited significantly low prevalence of severe PVWMLs (p = 0.001) and DWMLs (p = 0.001). After logistic regression was applied, severe WMLs predicted less favorable outcomes independently, compared with those with no to moderate PVWMLs and DWMLs [odds ratio (OR), 0.47; 95% confidence interval (CI), 0.25-0.87 for severe PVWMLs; OR, 0.40; 95% CI, 0.21-0.79 for severe DWMLs]. Conclusions: SVD is common in stroke patients with ATF. PVWMLs and DWMLs are independently associated with functional outcomes in stroke patients with ATF. The burden of SVD should be considered in future antiplatelet strategies for stroke patients after ATF.

The prescribing patterns of antithrombotic agents for prevention of recurrent ischemic stroke.

OBJECTIVES: Antithrombotic agents are effective in the secondary prevention of ischemic strokes. In the present study, we sought to determine the antithrombotic prescribing patterns of neurologists in patients with first-ever ischemic stroke and also to identify the factors influencing the choice of a specific agent and what changes are made when a recurrent stroke occurs in these patients. METHODS: We retrospectively reviewed the medical records of neurology patients who were diagnosed with first-ever ischemic stroke and were antithrombotic naive from January 1, 2000 to December 31, 2000. Patients' antithrombotic agents at discharge and during the follow-up period were reviewed to identify factors affecting the choice of antithrombotic agents. RESULTS: A total of 376 patients experienced non-fatal first-ever ischemic stroke. Of these, 351 were prescribed antithrombotic agents at discharge, while the remaining 25 were not on antithrombotic treatment. Low-dose aspirin was the most commonly prescribed agent (65%). The most important determinant for the choice of other antiplatelet agents was aspirin intolerance. Not surprisingly, only 36% of the patients with atrial fibrillation were treated with oral anticoagulants at the time of hospital discharge. CONCLUSION: Aspirin remains the most commonly used antithrombotic agent for the prevention of recurrent stroke among antithrombotic naive patients with a first-ever ischemic stroke in our institution. Our results demonstrate that current recommendations find their way into clinical practice, but to a limited extent. We aim that all patients discharged from our hospital after strokes must receive appropriate antithrombotic drugs for prevention of recurrent strokes provided if there are no contraindications to therapy.

Intravenous Thrombolysis Administration 3-4.5 h After Acute Ischemic Stroke: A Retrospective, Multicenter Study.

Background and Objectives: Intravenous recombinant tissue plasminogen activator (rt-PA) has been approved for acute ischemic stroke (AIS) within 3 h after onset and the treatment was then extended to 4.5 h. However, the Food and Drug Administration did not approve the indication in the expanded time window. This retrospective, matched cohort study aims to investigate the effectiveness and safety of rt-PA in AIS at 3-4.5 h after onset. Materials and Methods: The treatment group included AIS patients receiving rt-PA at 3-4.5 h after onset, otherwise complying with the regulation, in the stroke registries in 16 hospitals between 2008 and 2017. The control group included age- and sex-matched patients not receiving intravenous thrombolysis from the same registries, excluding those with contraindications. The primary outcome was modified Rankin Scale (mRS) 0-1 at day 90. The safety outcomes were any intracerebral hemorrhage (ICH), early neurological deterioration and 3-month mortality. Results: Each group had 374 patients. There were 34.0% of patients with 3-month mRS 0-1 in the treatment group vs. 22.7% in the control group with an odds ratio of 1.75 (95% confidence intervals, 1.27 to 2.42, P = 0.001). There was no difference in symptomatic ICH, early neurological deterioration and 3-month mortality rates between two groups. The 3-month mRS and symptomatic ICH did not differ significantly in patients receiving standard dose or low dose of rt-PA. Conclusions: Our results support the prescription of rt-PA in AIS patients 3-4.5 h after onset as an effective and tolerable treatment in their functional recovery.

Extrapontine myelinolysis after correction of hyponatremia presenting as generalized tonic seizures.

Central pontine myelinolysis and extrapontine myelinolysis are rare complications of rapid correction of chronic hyponatremia. Central pontine myelinolysis is more common and more predictable in presentation. Extrapontine myelinolysis' presenting symptoms vary and may be as general as lethargy or altered mood. We report experience with a patient who developed only extrapontine myelinolysis after rapid correction of severe hyponatremia associated with gastroenteritis. His presenting sign, generalized seizures, has not been previously reported. We summarize risk factors for myelinolysis, which may be more common than previously thought, as well as steps to minimize risk while managing vulnerable patients.

Ischaemic infarction masking aortic dissection: a pitfall to be avoided before thrombolysis.

Acute aortic dissection complicated by stroke is not uncommon but may be difficult to evaluate, especially in patients with impaired mental status. We report a patient who had evidence of an ischaemic stroke but was fortuitously not given thrombolytic treatment. She was subsequently found to have an extensive aortic dissection involving both carotid arteries. The decision of whether to give thrombolytic treatment is understandably an urgent one, but careful attention should be paid to subtle signs and symptoms such as atypical chest pain and carotid bruits that might suggest aortic dissection, especially involving the carotid arteries. There should be a high index of suspicion for acute aortic dissection in such cases and a low threshold for performing carotid ultrasound.

Hyperglycemia combined Helicobacter pylori infection increases risk of synchronous colorectal adenoma and carotid artery plaque.

BACKGROUND: Cardiovascular disease and colorectal cancer have severe consequences to human health and may occur simultaneously or sequentially. Carotid artery plaque is a predictor of cardiovascular disease, and colorectal adenoma is a premalignant lesion of colorectal cancer. We investigated the core risk factors of carotid artery plaque and colorectal adenoma. RESULTS: In total, 2361 subjects were enrolled. In multivariate analysis, age ≥ 60 years, male sex, BMI > 27, LDL > 130 mg/dL, HbA1c ≥ 6.5%, hs-CRP > 0.3 mg/L and H. pylori infection were independent risk factors for synchronous colorectal adenoma and carotid artery plaque formation. In the H. pylori-positive and -negative groups, the proportions and odds ratio (OR) for synchronous colon adenoma and carotid artery plaque increased with increasing HbA1c. OR for synchronous colon adenoma and carotid artery plaque was significantly higher in the participants with HbA1c levels of 5.7%-6.4% and HbA1c ≥ 6.5% than in those with normal HbA1c in the H. pylori-negative group. The OR was more significant increased for H. pylori-positive patients when HbA1c level ≥ 6.5% was 15.87 (95% CI 8.661-29.082, p < 0.0001). MATERIALS AND METHODS: The records of 4669 subjects aged > 40 years who underwent bidirectional gastrointestinal endoscopy and carotid artery ultrasound examination on the same day or within 12 months of endoscopy examination from January 2006 to December 2015 were reviewed. All subjects had a gastric biopsy specimen tested for Helicobacter pylori. CONCLUSIONS: Hyperglycemia combined with H. pylori infection was an increased risk factor for synchronous colorectal adenoma and carotid artery plaque formation. Diabetes control and H. pylori eradication may be warranted in higher prevalence areas.

Acute neurological deficits caused by cefipime: a case report and review of literature.

Cefepime (Maxipime) is a fourth-generation cephalosporin commonly used to treat a variety of infections. Its controversial side effect profile is not well appreciated by first-line practitioners. We report a case of urinary tract infection treated with cefepime in a 91-year-old woman. The acute onset of conscuous disturbance was noted on the 9th day of cefepime treatment. Computed tomogram and magnetic resonance image of the brain showed no specific findings. The neurological symptoms and signs such us conscious disturbance, ocular bobbing, asterexis disappeared after discontinuation of cefepime. We suggest that physicians should cefepime as a possible cause of reversible neurological deficits.

A case of bow hunter's stroke caused by non-dominant vertebral artery.

Rotational movements in the territory of vertebrobasilar artery of the head and neck can induce vertebrobasilar insufficiency (VBI) or infarction. The term "bow hunter's stroke" or "rotational VBI" has been used to describe this clinical syndrome. In most cases, symptoms were provoked because of involvement of a dominant vertebral artery (VA) with hypoplasia or occlusion of the contralateral VA. The author presented a case in which bow hunter's stroke was caused by occlusion of a non-dominant VA ending in the posterior inferior cerebellar artery (PICA). Diagnosis of rotational VBI was based on stereotypical clinical symptoms related to head rotation and hemodynamic study of the effects of head rotation. VA compression was documented in dynamic ultrasonography including the disappearance of end-diastolic flow in extracranial portion of VA and marked reduction in blood flow velocity (more than 50%) in the intracranial portion of VA upon head rotation. We emphasize that rotational occlusion of this anatomical variation is an important cause of VBI. This may cause permanent neurological deficits if left undiagnosed.

The Relationship among Carotid Artery Remodeling, Cardiac Geometry, and Serum N-Terminal Pro-B-Type Natriuretic Peptide Level in Asymptomatic Asians: Sex-Differences and Longitudinal GEE Study.

BACKGROUND: Carotid artery remodeling is known to be associated with a variety of cardiovascular diseases. However, there is limited information regarding gender differences in carotid remodeling. We sought to investigate the associations among blood pressure (BP), carotid artery remodeling and cardiac geometries, and further explore gender differences. MATERIALS AND METHODS: In a large cohort of asymptomatic adults undergoing routine health screening with repeated observations, we related measures of carotid artery diameter (CCAD) to various BP components, cardiac geometries and blood N-terminal pro-brain natriuretic peptide (NT-proBNP) level, both from baseline cross-sectional and longitudinal dataset using generalized estimating equations (GEE). RESULTS: A total of 2,914 person-visits (baseline: n=998, mean age: 47 ± 8.9 years, 34% female) were studied (median: 6 ± 1.73 years follow up). We observed that CCAD was larger in men (p<0.01) and positively related to baseline age or all blood pressure components (including systolic BP [SBP], diastolic BP [DBP] and pulse pressure [PP], all p<0.01) even after accounting for clinical covariates, which did not change significantly at follow up (repeat-visit longitudinal GEE models). At baseline, per each increased unit of CCAD was associated with elevated LV mass index (ß-coef: 6.72, with odds ratio [OR]: 1.47, 95% CI: 1.06 to 2.07 for ventricular hypertrophy; AUROC: 0.65, CCAD cut-off: 7.25mm) and NT-proBNP (ß-coef: 5.35, OR: 4.22, 95% CI: 1.42 to 12.6 for >=300pg/mL; AUROC: 0.79, CCAD cut-off: 7.95mm, all p<0.05), which remained significant in multi-variate and longitudinal models. There was a prominent sex interaction (p for interaction with age and systolic BP: 0.004 and 0.028 respectively), where the longitudinal associations of age and systolic BP with increasing CCAD as more pronounced in women than men. CONCLUSION: These data demonstrated that carotid artery remodeling may parallel subclinical biomarker of cardiac dysfunction, and further showed greater effects of aging and higher blood pressure on such remodeling process in women than men. Further study is warranted to understand how this predisposition of elderly hypertensive women to vascular remodeling may play a role in clinical settings.

The efficacy and safety of cilostazol in ischemic stroke patients with peripheral arterial disease (SPAD): protocol of a randomized, double-blind, placebo-controlled multicenter trial.

RATIONALE: It is not uncommon for patients with ischemic stroke to have peripheral arterial disease (PAD). Patients with polyvascular diseases carry greater burden of atherosclerosis and higher risks of developing vascular events and death. More effective regimens, such as dual antiplatelet agents, may be more effective for controlling progression of atherosclerosis in secondary prevention. AIM: This study aims to evaluate whether cilostazol plus aspirin is more efficacious than aspirin alone for preventing progression of atherosclerosis in patients with ischemic stroke or transient ischemic attack (TIA) who also have peripheral arterial disease. DESIGN: The Safety and Efficacy of Cilostazol in Ischemic Stroke Patients with Peripheral Arterial Disease (SPAD) study is a randomized double-blinded placebo-controlled trial. Patients with previous ischemic stroke or TIA who had been taking aspirin (100 mg per day), aged 50 years or older, with PAD in the lower limbs based on ankle-brachial index (ABI) <1·0 will be randomized into the treatment group with cilostazol (200 mg/day) or the placebo group on 1:1 basis. STUDY OUTCOMES: Patients will be evaluated at 1, 3, 6, 9 and 12 months after randomization. The primary endpoint is difference in change in ABI between groups. The secondary and tertiary endpoints are the difference between groups in change in carotid intima-media thickness (IMT) and incidence rate of major cardiovascular events, including recurrent stroke, myocardial infarction, unstable angina, other vascular events, and death; and the safety measures, including major bleeding events, hemorrhagic stroke and death of any cause. CONCLUSION: The SPAD trial is the first study to evaluate the safety and efficacy of dual antiplatelet agents, aspirin plus cilostazol, in comparison with aspirin alone in patients with both ischemic stroke or TIA and PAD. Results from this trial will provide important information on the merit of adding cilostazol to aspirin for slowing down progression of atherosclerosis in patients with ischemic stroke and PAD.