Cilostazol plus Aspirin vs. Clopidogrel plus Aspirin in Acute Minor Stroke or Transient Ischemic Attack.

AIM: This study compared the effectiveness, safety, and mortality risks between cilostazol plus aspirin and clopidogrel plus aspirin treatment for patients with acute minor ischemic stroke or transient ischemic attack (TIA). METHODS: This retrospective cohort study employed a new-user design and utilized data from the nationwide Health and Welfare Database in Taiwan. Patients were included if they were discharged with newly initiated cilostazol plus aspirin or clopidogrel plus aspirin after primary acute minor ischemic stroke or TIA hospitalization between 2009 and 2018. Inverse probability of treatment weighting was applied to balance covariates between study groups. Effectiveness outcomes were the risks of acute ischemic stroke, acute myocardial infarction (AMI), TIA, and composite cardiovascular events; Safety outcomes were the risks of intracranial hemorrhage (ICH), gastrointestinal bleeding, and composite bleeding events; Mortality outcomes were the risks of fatal stroke, cardiovascular mortality, and all-cause mortality. RESULTS: A total of 3,403 patients were included, of which 578 were treated with cilostazol plus aspirin and 2,825 were treated with clopidogrel plus aspirin. Cilostazol plus aspirin was associated with a higher risk of ICH (HR: 1.82; 95% CI: 1.16-2.84) compared to clopidogrel plus aspirin. No significant differences in the risks of effectiveness or mortality outcomes between the two groups were found. CONCLUSIONS: The effectiveness and mortality of the two groups were similar for patients with acute minor ischemic stroke or TIA. However, cilostazol plus aspirin was associated with a higher risk of ICH compared to clopidogrel plus aspirin. Patients treated with cilostazol plus aspirin among this population should be monitored carefully to ensure their safety.

Association between impaired dynamic cerebral autoregulation and BBB disruption in reversible cerebral vasoconstriction syndrome.

BACKGROUND: Half of the sufferers of reversible cerebral vasoconstriction syndrome (RCVS) exhibit imaging-proven blood-brain barrier disruption. The pathogenesis of blood-brain barrier disruption in RCVS remains unclear and mechanism-specific intervention is lacking. We speculated that cerebrovascular dysregulation might be associated with blood-brain barrier disruption in RCVS. Hence, we aimed to evaluate whether the dynamic cerebral autoregulation is altered in patients with RCVS and could be associated with blood-brain barrier disruption. METHODS: A cross-sectional study was conducted from 2019 to 2021 at headache clinics of a national tertiary medical center. Dynamic cerebral autoregulation was evaluated in all participants. The capacity of the dynamic cerebral autoregulation to damp the systemic hemodynamic changes, i.e., phase shift and gain between the cerebral blood flow and blood pressure waveforms in the very-low- and low-frequency bands were calculated by transfer function analysis. The mean flow correlation index was also calculated. Patients with RCVS received 3-dimensional isotropic contrast-enhanced T2 fluid-attenuated inversion recovery imaging to visualize blood-brain barrier disruption. RESULTS: Forty-five patients with RCVS (41.9 ± 9.8 years old, 29 females) and 45 matched healthy controls (41.4 ± 12.5 years old, 29 females) completed the study. Nineteen of the patients had blood-brain barrier disruption. Compared to healthy controls, patients with RCVS had poorer dynamic cerebral autoregulation, indicated by higher gain in very-low-frequency band (left: 1.6 ± 0.7, p = 0.001; right: 1.5 ± 0.7, p = 0.003; healthy controls: 1.1 ± 0.4) and higher mean flow correlation index (left: 0.39 ± 0.20, p = 0.040; right: 0.40 ± 0.18, p = 0.017; healthy controls: 0.31 ± 0.17). Moreover, patients with RCVS with blood-brain barrier disruption had worse dynamic cerebral autoregulation, as compared to those without blood-brain barrier disruption, by having less phase shift in very-low- and low-frequency bands, and higher mean flow correlation index. CONCLUSIONS: Dysfunctional dynamic cerebral autoregulation was observed in patients with RCVS, particularly in those with blood-brain barrier disruption. These findings suggest that impaired cerebral autoregulation plays a pivotal role in RCVS pathophysiology and may be relevant to complications associated with blood-brain barrier disruption by impaired capacity of maintaining stable cerebral blood flow under fluctuating blood pressure.

Role of the Autism Risk Gene Shank3 in the Development of Atherosclerosis: Insights from Big Data and Mechanistic Analyses.

Increased medical attention is needed as the prevalence of autism spectrum disorder (ASD) rises. Both cardiovascular disorder (CVD) and hyperlipidemia are closely associated with adult ASD. Shank3 plays a key genetic role in ASD. We hypothesized that Shank3 contributes to CVD development in young adults with ASD. In this study, we investigated whether Shank3 facilitates the development of atherosclerosis. Using Gene Set Enrichment Analysis software (Version No.: GSEA-4.0.3), we analyzed the data obtained from Shank3 knockout mice (Gene Expression Omnibus database), a human population-based study cohort (from Taiwan's National Health Insurance Research Database), and a Shank3 knockdown cellular model. Shank3 knockout upregulated the expression of genes of cholesterol homeostasis and fatty acid metabolism but downregulated the expression of genes associated with inflammatory responses. Individuals with autism had higher risks of hyperlipidemia (adjusted hazard ratio (aHR): 1.39; p < 0.001), major adverse cardiac events (aHR: 2.67; p < 0.001), and stroke (aHR: 3.55; p < 0.001) than age- and sex-matched individuals without autism did. Shank3 downregulation suppressed tumor necrosis factor-α-induced fatty acid synthase expression; vascular cell adhesion molecule 1 expression; and downstream signaling pathways involving p38, Jun N-terminal kinase, and nuclear factor-κB. Thus, Shank3 may influence the development of early-onset atherosclerosis and CVD in ASD. Furthermore, regulating Shank3 expression may reduce inflammation-related disorders, such as atherosclerosis, by inhibiting tumor necrosis factor-alpha-mediated inflammatory cascades.

Core and penumbra estimation using deep learning-based AIF in association with clinical measures in computed tomography perfusion (CTP).

OBJECTIVES: To investigate whether utilizing a convolutional neural network (CNN)-based arterial input function (AIF) improves the volumetric estimation of core and penumbra in association with clinical measures in stroke patients. METHODS: The study included 160 acute ischemic stroke patients (male = 87, female = 73, median age = 73 years) with approval from the institutional review board. The patients had undergone CTP imaging, NIHSS and ASPECTS grading. convolutional neural network (CNN) model was trained to fit a raw AIF curve to a gamma variate function. CNN AIF was utilized to estimate the core and penumbra volumes which were further validated with clinical scores. RESULTS: Penumbra estimated by CNN AIF correlated positively with the NIHSS score (r = 0.69; p < 0.001) and negatively with the ASPECTS (r = - 0.43; p < 0.001). The CNN AIF estimated penumbra and core volume matching the patient symptoms, typically in patients with higher NIHSS (> 20) and lower ASPECT score (< 5). In group analysis, the median CBF < 20%, CBF < 30%, rCBF < 38%, Tmax > 10 s, Tmax > 10 s volumes were statistically significantly higher (p < .05). CONCLUSIONS: With inclusion of the CNN AIF in perfusion imaging pipeline, penumbra and core estimations are more reliable as they correlate with scores representing neurological deficits in stroke. CRITICAL RELEVANCE STATEMENT: With CNN AIF perfusion imaging pipeline, penumbra and core estimations are more reliable as they correlate with scores representing neurological deficits in stroke.

The 2023 Taiwan Stroke Society Guidelines for the management of patients with intracranial atherosclerotic disease.

Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke, especially in Asian populations, which has a high risk of recurrent stroke and cardiovascular comorbidities. The present guidelines aim to provide updated evidence-based recommendations for diagnosis and management of patients with ICAD. Taiwan Stroke Society guideline consensus group developed recommendations for management of patients with ICAD via consensus meetings based on updated evidences. Each proposed class of recommendation and level of evidence was approved by all members of the group. The guidelines cover six topics, including (1) epidemiology and diagnostic evaluation of ICAD, (2) nonpharmacological management of ICAD, (3) medical therapy for symptomatic ICAD, (4) endovascular thrombectomy and rescue therapy for acute ischemic stroke with underlying ICAD, (5) endovascular interventional therapy for postacute symptomatic intracranial arterial stenosis, and (6) surgical treatment of chronic symptomatic intracranial arterial stenosis. Intensive medical treatment including antiplatelet therapy, risk factor control, and life style modification are essential for patients with ICAD.

Monogenic Causes in Familial Stroke Across Intracerebral Hemorrhage and Ischemic Stroke Subtypes Identified by Whole-Exome Sequencing.

Whole exome sequencing (WES) has been used to detect rare causative variants in neurological diseases. However, the efficacy of WES in genetic diagnosis of clinically heterogeneous familial stroke remains inconclusive. We prospectively searched for disease-causing variants in unrelated probands with defined familial stroke by candidate gene/hotspot screening and/or WES, depending on stroke subtypes and neuroimaging features at a referral center. The clinical significance of each variant was determined according to the American College of Medical Genetics guidelines. Among 161 probands (mean age at onset 53.2 ± 13.7 years; male 63.4%), 33 participants (20.5%) had been identified with 19 pathogenic/likely pathogenic variants (PVs; WES applied 152/161 = 94.4%). Across subtypes, the highest hit rate (HR) was intracerebral hemorrhage (ICH, 7/18 = 38.9%), particularly with the etiological subtype of structural vasculopathy (4/4 = 100%, PVs in ENG, KRIT1, PKD1, RNF213); followed by ischemic small vessel disease (SVD, 15/48 = 31.3%; PVs in NOTCH3, HTRA1, HBB). In contrast, large artery atherosclerosis (LAA, 4/44 = 9.1%) and cardioembolism (0/11 = 0%) had the lowest HR. NOTCH3 was the most common causative gene (16/161 = 9.9%), presenting with multiple subtypes of SVD (n = 13), ICH (n = 2), or LAA (n = 1). Importantly, we disclosed two previously unreported PVs, KRIT1 p.E379* in a familial cerebral cavernous malformation, and F2 p.F382L in a familial cerebral venous sinus thrombosis. The contribution of monogenic etiologies was particularly high in familial ICH and SVD subtypes in our Taiwanese cohort. Utilizing subtype-guided hotspot screening and/or subsequent WES, we unraveled monogenic causes in 20.5% familial stroke probands, including 1.2% novel PVs. Genetic diagnosis may enable early diagnosis, management and lifestyle modification. Among 161 familial stroke probands, 33 (20.5%) had been identified pathogenic or likely pathogenic monogenic variants related to stroke. The positive hit rate among all subtypes was high in intracerebral hemorrhage (ICH) and ischemic small vessel disease (SVD). Notably, two previously unreported variants, KRIT1 p.E379* in a familial cerebral cavernous malformation and F2 p.F382L in familial cerebral venous sinus thrombosis, were disclosed. CVT cerebral venous thrombosis; HTN Hypertensive subtype; LAA large artery atherosclerosis; SV structural vasculopathy; U Undetermined.

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.

Vascular function in the aging human brain during muscle exertion.

To determine how brain oxygenation is stably maintained during advancing age, cerebral oxygenation and hemoglobin were measured real-time at 10 Hz using near-infrared spectroscopy (NIRS) at rest (30 seconds) and during a 10-repeated handgrip strength test (30 seconds) for 834 adults (M/F = 45/55%) aged 20-88 y. The amplitude of cerebral hemodynamic fluctuation was reflected by converting 300 values of % oxygen saturation and hemoglobin of each 30-second phase to standard deviation as indicatives of brain oxygenation variability (BOV) and brain hemodynamic variability (BHV) for each participant. Both BOV (+21-72%) and BHV (+94-158%) increased during the maximal voluntary muscle exertions for all age levels (α < 0.05), suggesting an increased vascular recruitment to maintain oxygen homeostasis in the brain. Intriguingly, BHV was >100 folds for both resting and challenged conditions (α < 0.001) in >80% of adults aged above 50 y despite similar BOV compared with young age counterparts, indicating a huge cost of amplifying hemodynamic oscillation to maintain a stable oxygenation in the aging brain. Since vascular endothelial cells are short-lived, our results implicate a hemodynamic compensation to emergence of daily deficits in replacing senescent endothelial cells after age 50 y.

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.

Associations Between Cerebral Vasoreactivity and Cognitive Function in the Middle-Aged Non-Demented Population.

BACKGROUND: Increasing evidence shows early vascular dysregulation in the pathophysiology of Alzheimer's disease (AD) in elderly population. OBJECTIVE: We wondered about the relationship between vascular health and cognitive performance in middle-aged adults. The present study aims to evaluate whether and which brain vascular hemodynamic parameters are associated with cognitive functions in a middle-aged, non-demented population. METHODS: We recruited 490 middle-aged community-based participants (30-60 years). Transcranial color-coded sonography was used to measure cerebral vascular hemodynamics, including mean flow velocity, pulsatility index, and breath-holding index (BHI) in the middle cerebral arteries (MCAs). Cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA). A multivariate linear regression model was used to determine the association between the MoCA scores and each intracranial hemodynamic parameter. RESULTS: In 369 participants (median age 52 years [IQR 47-56], 48.8% men) with robust acoustic windows, the factors related to poorer MoCA scores were older age, less education extent, and the habitats of cigarette smoking or alcohol consumption. Multivariate analyses did not show a significant association between any intracranial hemodynamic parameters in both MCAs and MoCA scores in the total study population. Left MCA BHI was found to be significantly and independently correlated with the MoCA scores only in people aged 55-60 years (n = 111, B = 0.70, 95% confidence interval, 0.13-1.26, p = 0.017), however, not in people younger than 55 years. CONCLUSION: Our results emphasize the role of neurovascular abnormalities in the early pathophysiology of cognitive impairment and suggest cerebral vasoreactivity as the earliest detectable cognition-associated hemodynamic parameter.

Application of hyperglycemia/diabetes-derived polygenic risk scores on the risk of poor outcomes after an ischemic stroke.

BACKGROUND: Unfavorable prognoses are often accompanied for hyperglycemic stroke patients. This study aimed to construct a hyperglycemia/diabetes-derived polygenic risk score (PRS) to improve the predictive performance for poor outcome risks after a stroke and to evaluate its potential clinical application. METHODS: A hospital-based cohort study was conducted including 1320 first-ever acute ischemic stroke (AIS) patients and 1210 patients who completed the follow-up at 3 months. PRSs were calculated for hyperglycemia/diabetes mellitus using results from genome-wide association studies in Asians. An unfavorable functional outcome was defined as a modified Rankin Scale score of ≥3 at 3, 6, and 12 months of follow-up. The prediction of a poor prognosis was evaluated using measures of model discrimination, calibration, and net reclassification improvement (NRI). RESULTS: The second to fourth PRS quartiles (≥Q2) were significantly associated with higher risks of unfavorable outcomes at 3 months compared with the first quartile as the reference group after adjusting for age, baseline stroke severity, hypertension, diabetes, dyslipidemia, smoking, heart disease, and ischemic stroke subtype (p for trend <0.0001). The addition of the PRS to traditional risk predictors of poor outcomes after an AIS significantly improved the model fit (likelihood ratio test p < 0.0001) and enhanced measures of reclassification (NRI, 0.245; 95% confidence interval [CI], 0.195-0.596). The corrected C-index for the PRS combining traditional risk factors at 3 months after a stroke was 0.899 (95% CI, 0.878-0.980). Among hyperglycemic AIS patients, those who did not take an antidiabetic drug and whose PRS was ≥Q2 had higher risks of an unfavorable outcome at 3 months compared with patients who took the medicine. CONCLUSION: The hyperglycemia/diabetes-derived PRS was associated with poor outcomes after an AIS, but further studies are needed to validate its use for clinical applications.

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.

Untargeted metabolomics predicts the functional outcome of ischemic stroke.

BACKGROUND/PURPOSE: Metabolites in blood have been found associated with the occurrence of vascular diseases, but its role in the functional recovery of stroke is unclear. The aim of this study is to investigate whether the untargeted metabolomics at the acute stage of ischemic stroke is able to predict functional recovery. METHODS: One hundred and fifty patients with acute ischemic stroke were recruited and followed up for 3 months. Fasting blood samples within 7 days of stroke were obtained, liquid chromatography and mass spectrometry were applied to identify outcome-associated metabolites. The patients' clinical characteristics and identified metabolites were included for constructing the outcome prediction model using machine learning approaches. RESULTS: By using multivariate analysis, 220 differentially expressed metabolites (DEMs) were discovered between patients with favorable outcomes (modified Rankin Scale, mRS ≤ 2 at 3 months, n = 77) and unfavorable outcomes (mRS ≥ 3 at 3 months, n = 73). After feature selection, 63 DEMs were chosen for constructing the outcome prediction model. The predictive accuracy was below 0.65 when including patients' clinical characteristics, and could reach 0.80 when including patients' clinical characteristics and 63 selected DEMs. The functional enrichment analysis identified platelet activating factor (PAF) as the strongest outcome-associated metabolite, which involved in proinflammatory mediators release, arachidonic acid metabolism, eosinophil degranulation, and production of reactive oxygen species. CONCLUSION: Metabolomics is a potential method to explore the blood biomarkers of acute ischemic stroke. The patients with unfavorable outcomes had a lower PAF level compared to those with favorable outcomes.

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.

Efficacy and safety of clopidogrel and aspirin do not differ in patients with stable ischemic stroke.

BACKGROUND: The current study compared the efficacy and safety of clopidogrel vs aspirin in the secondary prevention of ischemic stroke (IS). METHODS: We included patients from the Taiwan National Health Insurance Research Database who were aged between 20 and 80 years, had their first ever IS, had no diagnosis of atrial fibrillation, and had not used an oral anticoagulant before the index IS between 2002 and 2010. We excluded patients who died or were admitted to a hospital due to acute myocardial infarction, recurrent IS, or major bleeding within 3 months of IS. Patients were then classified into clopidogrel as aspirin users. Propensity score matching was adopted to select clopidogrel and aspirin groups with similar baseline characteristics (n = 8457 vs 16,914, mean follow-up period of 2.1 years and 1.9 years, respectively). Conditional Cox proportional hazard regression was used to compare risks of all-cause death, cardiovascular death, recurrent stroke, acute myocardial infarction, and major bleeding in clopidogrel users and aspirin users. RESULTS: The risks of all-cause death, cardiovascular death, recurrent stroke, and acute myocardial infarction did not differ between clopidogrel and aspirin users. Subgroup analyses revealed that the results were consistent regardless of age, disease severity, or comorbidity. CONCLUSION: According to real-world data, the efficacy and safety of clopidogrel and aspirin for secondary prevention of stable IS did not differ.

Impaired cerebral autoregulation is associated with poststroke cognitive impairment.

OBJECTIVE: To investigate whether dynamic cerebral autoregulation (CA) and neuroimaging characteristics are determinants of poststroke cognitive impairment (PSCI). METHODS: Eighty patients within 7 days of acute ischemic stroke and 35 age- and sex-matched controls were enrolled. In the patients with stroke, brain magnetic resonance imaging and dynamic CA were obtained at baseline, and dynamic CA was followed up at 3 months and 1 year. Montreal Cognitive Assessment (MoCA) was performed at 3 months and 1 year. Patients with a MoCA score <23 at 1 year were defined as having PSCI, and those with a MoCA score that decreased by 2 points or more between the 3-month and 1-year assessments were defined as having progressive cognitive decline. RESULTS: In total, 65 patients completed the study and 16 developed PSCI. The patients with PSCI exhibited poorer results for all cognitive domains than did those without PSCI. The patients with PSCI also had poorer CA (lower phase shift between cerebral blood flow and blood pressure waveforms in the very low frequency band) compared with that of the patients without PSCI and controls at baseline and 1 year. CA was not different between the patients without PSCI and controls. In the multivariate analysis, low education level, lobar microbleeds, and impaired CA (very low frequency phase shift [≤46°] within 7 days of stroke), were independently associated with PSCI. In addition, impaired CA was associated with progressive cognitive decline. INTERPRETATION: Low education level, lobar microbleeds, and impaired CA are involved in the pathogenesis of PSCI.

Protective effects of ischemic preconditioning against neuronal apoptosis and dendritic injury in the hippocampus are age-dependent.

Ischemic preconditioning with non-lethal ischemia can be protective against lethal forebrain ischemia. We hypothesized that aging may aggravate ischemic susceptibility and reduce brain plasticity against preconditioning. Magnetic resonance diffusion tensor imaging (DTI) is a sensitive tool to detect brain integrity and white matter architecture. This study used DTI and histopathology to investigate the effect of aging on ischemic preconditioning. In this study, adult and middle-aged male Mongolian gerbils were subjected to non-lethal 5-min forebrain ischemia (ischemic preconditioning) or sham-operation, followed by 3 days of reperfusion, and then lethal 15-min forebrain ischemia. A 9.4-Tesla MR imaging system was used to study DTI indices, namely fractional anisotropy (FA), mean diffusivity (MD), and intervoxel coherence (IC) in the hippocampal CA1 and dentate gyrus (DG) areas. In situ expressions of microtubule-associated protein 2 (MAP2, dendritic marker protein) and apoptosis were also examined. The 5-min ischemia did not cause dendritic and neuronal injury and any significant change in DTI indices and MAP2 in adult and middle-aged gerbils. The 15-min ischemia-induced significant delayed neuronal apoptosis and early dendritic injury evidenced by DTI and MAP2 studies in both CA1 and DG areas with more severe injury in middle-aged gerbils than adult gerbils. Ischemic preconditioning could improve neuronal apoptosis in CA1 area and dendritic integrity in both CA1 and DG areas with better improvement in adult gerbils than middle-aged gerbils. This study thus suggests an age-dependent protective effect of ischemic preconditioning against both neuronal apoptosis and dendritic injury in hippocampus after forebrain ischemia.

Systematic Review and Meta-Analysis of Home-Based Rehabilitation on Improving Physical Function Among Home-Dwelling Patients With a Stroke.

OBJECTIVE: To evaluate the effects of home-based rehabilitation on improving physical function in home-dwelling patients after a stroke. DATA SOURCES: Various electronic databases, including PubMed, Cumulative Index to Nursing and Allied Health, Embase, the Cochrane Central Register of Controlled Trials, and 2 Chinese data sets (ie, Chinese Electronic Periodical Services and China Knowledge Resource Integrated) were searched for studies published before March 20, 2019. STUDY SELECTION: Randomized controlled trials conducted to examine the effect of home-based rehabilitation on improving physical function in home-dwelling patients with a stroke and published in English or Chinese were included. In total, 49 articles in English (n=23) and Chinese (n=26) met the inclusion criteria. DATA EXTRACTION: Data related to patient characteristics, study characteristics, intervention details, and outcomes were extracted by 2 independent reviewers. DATA SYNTHESIS: A random-effects model with a sensitivity analysis showed that home-based rehabilitation exerted moderate improvements on physical function in home-dwelling patients with a stroke (g=0.58; 95% CI, 0.45∼0.70). Moderator analyses revealed that those patients with stroke of a younger age, of male sex, with a first-ever stroke episode, in the acute stage, and receiving rehabilitation training from their caregiver showed greater improvements in physical function. CONCLUSIONS: Home rehabilitation can improve functional outcome in survivors of stroke and should be considered appropriate during discharge planning if continuation care is required.