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Purpose: Carotid artery web (CaW) is a rare focal fibromuscular dysplasia that can lead to embolic strokes with large vessel occlusion. This condition can be effectively treated with endovascular thrombectomy (EVT). Our study aims to assess the prevalence of CaW among patients with acute ischemic stroke (AIS) who underwent EVT and to compare the clinical characteristics of CaW with other carotid artery pathologies. Methods: We enrolled consecutive patients with AIS who underwent EVT at a single medical center and two regional teaching hospitals in Taiwan from September 2014 to December 2021. We compared CaW with carotid dissection (CaD) and carotid large artery atherosclerosis (CaLAA) in terms of patient demographics and thrombus histological findings. Results: Of the 576 AIS patients who underwent EVT, four (mean age: 50 years) were diagnosed with CaW, resulting in a prevalence of 0.69%. Among these four patients, three experienced successful reperfusion after EVT and achieved functional independence (defined as a modified Rankin Scale score ≤2) three months post-stroke. Importantly, none of the CaW patients suffered a recurrent stroke within one year. Patients with CaW were younger than those with CaD or CaLAA, and exhibited fewer vascular risk factors. Additionally, CaW was associated with distal occlusion sites. The thrombus composition in CaW patients was similar to that in CaD patients. Conclusion: In conclusion, CaW is a rare finding among Asian patients with carotid artery disease who undergo for AIS. It is more prevalent in younger patients with a limited number of vascular risk factors.

Background: This study aimed to evaluate the performance of a modified U.S. (MUS) model for risk prediction of cardiovascular (CV) events in Asian patients and compare it to European and Japanese models. Methods: The MUS model, based on the US ACC/AHA 2018 lipid treatment guideline, was employed to stratify patients under primary or secondary prevention. Two multi-center prospective observational registry cohorts, T-SPARCLE and T-PPARCLE, were used to validate the scoring system, and the primary outcome was the time to first occurrence/recurrence of major adverse cardiac events (MACEs). The MUS model's performance was compared to other models from Europe and Japan. Results: A total of 10,733 patients with the mean age of 64.2 (SD: 11.9) and 36.5% female were followed up for a median of 5.4 years. The MUS model was validated, with an AUC score of 0.73 (95% CI 0.68–0.78). The European and Japanese models had AUC scores ranging from 0.6 to 0.7. The MUS model categorized patients into four distinct CV risk groups, with hazard ratios (HRs) as follows: very high- vs. high-risk group (HR = 1.91, 95% CI 1.53–2.39), high- vs. moderate-risk group (HR = 2.08, 95% CI 1.60–2.69), and moderate- vs. low-risk group (HR = 3.14, 95% CI 1.63–6.03). After adjusting for the MUS model, a history of atherosclerotic vascular disease (ASCVD) was not a significant predictor of adverse cardiovascular outcomes within each risk group. Conclusion: The MUS model is an effective tool for risk stratification in Asian patients with and without ASCVD, accurately predicting MACEs and performing comparably or better than other established risk models. Our findings suggest that patient management should focus on background risk factors instead of solely on primary or secondary prevention.

Background/purpose: Amiodarone increases exposure of direct oral anticoagulants (DOACs). We aimed to analyze the effects of concurrent amiodarone use on DOAC concentrations and clinical outcomes. Methods: Patients who were ≥20 years of age, had atrial fibrillation, and took DOAC were enrolled to provide trough and peak samples for DOAC concentration measurements using ultra-high-performance liquid chromatography-tandem mass spectrometry. The results were compared with concentrations reported in clinical trials to define above, within, or under the expected range. The outcomes of interest were major bleeding and any gastrointestinal bleeding. Multivariate logistic regression and Cox proportional hazards model were used to determine the impact of amiodarone on above-range concentration and clinical outcomes, respectively. Results: A total of 722 participants (420 men, 58.2%) were enrolled to provide 691 trough samples and 689 peak samples. Among them, 21.3% concurrently used amiodarone. The proportion of patients with above-range trough and peak concentrations was 16.4% and 30.2%, respectively, for amiodarone users, in contrast to 9.4% and 19.8% for amiodarone non-users. The use of amiodarone was associated with above-range trough and peak concentrations (odds ratio [OR] = 2.00 [1.16, 3.47] and 1.82 [1.19, 2.79], respectively). However, amiodarone was not a significant predictor of major bleeding or any gastrointestinal bleeding. Conclusion: Concurrent amiodarone use led to increased DOAC concentration but was not associated with a higher risk of major bleeding or any gastrointestinal bleeding. Therapeutic monitoring of DOAC users concurrently taking amiodarone may be recommended for patients with an additional risk of increased DOAC exposure.

Background: Long-chain ceramides are associated with the mechanisms and clinical outcomes of acute ischemic stroke (AIS). This study aimed to investigate the plasma ceramides and sphingosine-1-phosphate in AIS patients undergoing endovascular thrombectomy (EVT) and their associations with outcomes. Methods: Plasma samples were collected from 75 AIS patients who underwent EVT before (T1), immediately after (T2), and 24 h after (T3) the procedures and 19 controls that were matched with age, sex, and co-morbidities. The levels of ceramides with different fatty acyl chain lengths and sphingosine-1-phosphate were measured by UHPLC–ESI–MS/MS. A poor outcome was defined as a modified Rankin Scale score of 3–6 at 3 months after stroke. Results: The plasma levels of long-chain ceramides Cer (d18:1/16:0) at all three time points, Cer (d18:1/18:0) at T1 and T3, and Cer (d18:1/20:0) at T1 and very-long-chain ceramide Cer (d18:1/24:1) at T1 were significantly higher in AIS patients than those in the controls. In contrast, the plasma levels of sphingosine-1-phosphate in AIS patients were significantly lower than those in the controls at all three time points. Among the AIS patients, 34 (45.3%) had poor functional outcomes at 3 months poststroke. Multivariable analysis showed that higher levels of Cer (d18:1/16:0) and Cer (d18:1/18:0) at all three time points, Cer (d18:1/20:0) at T1 and T2, and Cer (d18:1/24:0) at T2 remained significantly associated with poor functional outcomes after adjustment for potential confounding factors. Conclusion: Plasma ceramides were elevated early in AIS patients with acute large artery occlusion. Furthermore, Cer (d18:1/16:0) and Cer (d18:1/18:0) could be early prognostic indicators for AIS patients undergoing EVT.

Hereditary cerebral cavernous malformations (CCMs) are characterized by clustered dilated capillary-like vessels in the brain. Autosomal dominant polycystic kidney disease (PKD) is characterized by renal cysts and extra-renal abnormalities. We report a Taiwanese family in which the index case exhibited coexisting phenotypes of both CCMs and PKD. The index case was a 55-year-old woman with known PKD who developed an intracerebral hemorrhage (ICH) in the right medulla. Neuroimaging revealed numerous microbleeds in the bilateral cerebrum and cerebellum. Radiological CCMs were suspected given the absence of other imaging markers of small vessel disease. A comprehensive panel of 183 cerebral vascular malformation genes were investigated through genome sequencing. A novel CCM2 frameshift variant (c.607_608delCT, p.Leu203Valfs∗53) causing a pathogenic premature stop codon, and a known PKD2 nonsense variant (c.2407C > T, p.Arg803∗), were found. Segregation analysis revealed that four siblings were affected by either isolated aforementioned PKD2 or CCM2 variant. Notably, radiological CCMs were exclusively found in siblings who had this CCM2 variant, and bilateral internal carotid artery aneurysms were restricted to one sibling who had the PKD2 variant but not the CCM2 variant. Our study expands the genetic spectrum of CCM2 and demonstrates unambiguous cosegregation of CCM2 and PKD2 variants with their respective phenotypes.

The previously published 2017 Taiwan Lipid Guidelines for High Risk Patients becomes the standard guidance of dyslipidemia management for patients with atherosclerotic cardiovascular disease (ASCVD) in Taiwan. New clinical trials of lipid lowering therapy were published successively after 2017. The study results changed the treatment concept of ASCVD. Therefore, an update focusing on the lipid treatment strategy for patients with ASCVD becomes necessary. In this focused update of the 2017 guideline, the treatment targets of low-density lipoprotein cholesterol (LDL-C) for patients with ASCVD were modified. The algorithm of LDL-C lowering therapy was revised. The recommendations in this focused update were made mainly based on the scientific evidence from recently published clinical trials and endorsed by the major medical societies in Taiwan.

Background/Purpose: Several risk scores have been developed to predict symptomatic intracerebral hemorrhage (SICH) after acute reperfusion therapy for ischemic stroke. We compared the performance of established risk scores in predicting SICH after EVT under different SICH criteria. Methods: A total of 258 patients with anterior circulation large vessel occlusion who received EVT in two medical centers of Taiwan were recruited. Three definitions of SICH, the European Collaborative Acute Stroke Study II (ECASS II), ECASS III, and the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), were used. The HAT, SITS-SICH, SEDAN, and TAG risk scores were applied. Logistic regression and area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of each risk model. Results: In the 258 included patients (mean age, 71.9 ± 11.8 years; men, 48.1%), the observed rates of SICH according to ECASS II, ECASS III, and SITS-MOST criteria were 10.1%, 5.0%, and 4.7%, respectively. Higher glucose level (>160 mg/dL) and unsuccessful recanalization independently predicted SICH under all criteria. Among the different risk scores, only SEDAN and TAG consistently predicted SICH. SEDAN and TAG scores exhibited the highest AUC in predicting SICH for ECASS III (SEDAN 0.72, TAG 0.72) and SITS-MOST (SEDAN 0.73, TAG 0.70) criteria. Conclusion: Among various risk scores, the TAG and SEDAN scores best predict SICH after EVT. Higher glucose level and unsuccessful recanalization, which are included in the TAG and SEDAN scores, are independent risk factors of SICH in the present cohort, highlighting their detrimental effects.

Background/Purpose: Recently optimized models for selecting the locations of hospitals capable of providing endovascular thrombectomy (EVT) did not consider the accuracy of the prehospital stroke scale assessment and possibility of secondary transport. Our study aimed to propose a new model for selecting existing hospitals with intravenous thrombolysis capability to become EVT-capable hospitals. Methods: A sequential order was provided to upgrade hospitals providing intravenous thrombolysis, using a mixed integer programming model based on current medical resource allocation. In addition, we drafted a centralized plan to redistribute existing EVT resources by redetermining locations of EVT-capable hospitals. Using historical data of 7679 on-scene patients with suspected stroke, the model was implemented to determine the hospital that maximizes the number of patients receiving EVT treatment within call-to-definitive-treatment time. Results: All suspected stroke patients were sent to EVT-capable hospitals directly under the current medical resource allocation model. After upgrading one additional hospital to become an EVT-capable hospital, the percentage of patients receiving definitive treatment within the standard call-to-definitive-treatment time was elevated from 68.82% to 72.97%. In the model, assuming that there is no hospital providing EVT, all patients suspected of stroke will be sent to EVT-capable hospitals directly after upgrading three or more hospitals to be able to provide treatment. Conclusion: All patients eligible for acute stroke treatment are sent to EVT-capable hospitals in the simulation under the current medical resource allocation model. This model can be utilized to provide insights for capacity redistribution in other regions.

Background/Purpose: Sphingolipids are major constituents of eukaryotic cell membranes and play key roles in cellular regulatory processes. Our recent results in an experimental stroke animal model demonstrated changes in sphingolipids in response to acute ischemic brain injury. This study aimed to investigate the plasma levels of sphingosine-1-phosphate (S1P) and ceramides in acute ischemic stroke (AIS) patients and their associations with functional outcomes. Methods: Plasma samples were collected from patients with AIS at

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.

Background/purpose: Atrial fibrillation (AF) patients with a history of ischemic stroke or transient ischemic attack (TIA) carry excessive risk of recurrent stroke. Real-world data for the Asian population is scarce. This study aimed to investigate the thromboembolism and major bleeding risk of non-vitamin K antagonist oral anticoagulant (NOAC) therapy among Asian patients, and to identify the risk factors of recurrent stroke. Methods: This retrospective study recruited AF patients aged over 20 years, who had a previous stoke or TIA, and received NOAC therapy. Thromboembolic events were recurrent ischemic stroke or TIA, and the major bleeding events were classified according to the PLATO (Platelet Inhibition and Patient Outcomes) criteria. Results: A total of 361 patients (61.2% male) were enrolled for data analysis. The incidence rate for recurrent ischemic stroke or TIA was 3.6 (95% CI = 2.5 to 5.5) per 100 person-years, and 0.9 (95% CI = 0.4 to 1.7) per 100 person-years for major bleeding. Patients with recurrent ischemic stroke or TIA were more likely to have malignancy (hazard ratio [HR] for malignancy = 4.4, 95% CI = 1.9 to 10.3, p = 0.001) and concomitantly take enzyme inducing antiepileptic drugs (EIAED, HR = 8.1, 95% CI = 2.7 to 24.1, p

Background: The application of non-vitamin K antagonist oral anticoagulant (NOAC) reduces the risk of intracerebral hemorrhage (ICH) in comparison with vitamin K antagonist (VKA). However, the features and outcomes of NOAC-associated ICH are still unclear, especially for Asian populations. Methods: We retrospectively analyzed 49 consecutive patients who had spontaneous ICH while using NOAC or VKA. We compared the clinical characteristics, ICH volume, 7-day and 3-month mortality, and functional outcomes at discharge and 3 months post-stroke using the modified Rankin Scale (mRS) between NOAC- and VKA-associated ICH. The clinical features, ICH volume, ICH location, and/or treatment methods were statistically adjusted. Results: Among the 49 ICH patients, 15 (30.6%) were using NOAC and 34 (69.4%) were taking VKA. There were no significant differences in the initial ICH volume between groups (mean volume 34.2 ± 43.8 vs. 59.4 ± 46.5 mL, p = 0.061). The percentage of early mortality (within 7 days post-ICH) was significantly lower in the NOAC group (13.3% vs. 44.1%; p = 0.047), but the 3-month mortality was similar (33.3% vs. 47.1%; p = 0.294). The functional outcome was equally poor in both groups at discharge (p = 0.670) and 3 months post-ICH (mean mRS score 4.7 ± 1.3 vs. 4.6 ± 1.7, p = 0.766). Conclusion: There were no significant differences in initial ICH volume, 90-day mortality, or functional outcomes between NOAC and VKA-associated ICH in Asians. Keywords: Intracerebral hemorrhage, Non-vitamin K antagonist oral anticoagulant, Outcome, Vitamin K antagonist

Background/purpose: Dabigatran is effective in preventing ischemic stroke and systemic embolism in patients with atrial fibrillation. Although the therapeutic window for dabigatran is wide, its pharmacokinetic properties can differ between specific populations. This study aimed to establish a real-life plasma dabigatran concentration database and investigate potential factors affecting this concentration in Asians. Methods: Patients under dabigatran therapy were recruited. Plasma dabigatran concentration was determined in trough and peak blood samples by using ultra-high performance liquid chromatography with tandem mass spectrometry analysis. Factors affecting the dabigatran concentration were investigated. Results: A total of 46 patients (33 male, 71.7%) were prospectively enrolled. Most of them were receiving a low dose regimen (110 mg twice daily, n = 38, 82.6%). The trough and peak concentrations were significantly correlated (p 3 points, and HAS-BLED score ≥3 points. Multiple linear regression analysis identified body weight and serum creatinine as key factors predicting trough concentration (p = 0.003 and 0.005, respectively). Importantly, drug adherence was the only independent factor associated with low trough concentration, defined as the lowest 20th percentile in our study cohort (n = 10, hazard ratio = 9.07; 95% CI, 1.12 to 73.22; p = 0.004). Conclusion: Dabigatran monitoring may be considered for patients at risk of overexposure, especially those with low body weight and renal insufficiency, and also for detecting those with extremely low drug concentration. Keywords: Adherence, Atrial fibrillation, Dabigatran, Drug concentration, Ischemic stroke, Pharmacokinetics

Background/purpose: Details of the communication between the caller and dispatcher have not been reported previously in Taiwan. This study aimed to: (1) understand the details of the communication between the caller and dispatcher among the calls for stroke patients, (2) identify factors associated with stroke recognition by dispatchers, and (3) evaluate the association between stroke recognition by dispatchers and stroke management. Methods: We conducted a retrospective observational study involving patients with stroke or transient ischemic stroke transported by the emergency medical service, and arriving at 9 hospitals in Taipei within 3 h of symptom onset from January 1, 2013 to February 28, 2014. Patients were excluded if tape-recording data or prehospital information were not available. Data of the enrolled patients were reviewed. We used stroke dispatch determination as the surrogate for stroke recognition by dispatchers. Multivariable logistic regression was used to identify the factors associated with stroke dispatch determination. Results: A total of 507 patients were included. In approximately 50% of cases, callers were close family members. Ninety-one patients (17.9%) had stroke dispatch determination. After adjustment, stroke reported spontaneously, any symptom included in the Cincinnati Prehospital Stroke Scale reported spontaneously, and dispatcher adherence to the protocol, were associated with stroke dispatch determination significantly. Stroke dispatch determination was associated with receiving pre-arrival notification, shorter door-to-computed tomography time, and thrombolytic therapy. Conclusion: The dispatchers should spend more time identifying stroke patients by following the dispatch protocol. Recognition of stroke by dispatchers was associated with improved stroke care. Keywords: Stroke, Dispatch, Thrombolytic therapy

Background/purpose: Endovascular thrombectomy has been strongly recommended for treatment of acute ischemic stroke (AIS) with large vessel occlusion. This study aimed to evaluate its efficacy and safety in an Asian population from a single center in Taiwan. Methods: Patients who experienced AIS and received endovascular thrombectomy during the period of September 2014 to September 2016 at National Taiwan University Hospital were included. Factors related to favorable outcome, defined as modified Rankin scale 0–2 at 90 days after stroke, were analyzed. Results: During the study period, 65 patients (mean age, 71.9 ± 12.4 years; 44.6% females) received endovascular thrombectomy, including 33 who received intravenous thrombolysis before the endovascular treatment. A significant trend of increasing thrombectomy therapy was observed. The median National Institutes of Health Stroke Scale (NIHSS) score on admission was 19 (interquartile range, 15–26). The sites of vessel occlusion were middle cerebral artery in 47 (72.3%) patients, intracranial internal carotid artery in 8 (12.4%), anterior cerebral artery in 1 (1.5%), and basilar artery in 9 (13.8%). The median times from stroke onset to groin puncture and from groin puncture to recanalization time were 200 and 29.5 min, respectively. Successful revascularization was achieved in 41 (63.1%) patients. Two (3.1%) patients had symptomatic hemorrhagic transformation. At 90 days, 25 (38.5%) patients achieved favorable outcome. A shorter time from onset to puncture, and successful recanalization were independent predictors of favorable outcome. Conclusion: This study demonstrated the therapeutic promise of endovascular thrombectomy for treatment of AIS with large vessel occlusion in a clinical setting. Keywords: Acute ischemic stroke, Outcome, Thrombectomy, Thrombolysis

Background: Enhancing detection of undiagnosed atrial fibrillation (AF) in hospitalized patients with a recent ischemic stroke is important because of the treatment implications; especially since presence of paroxysmal AF may not be picked up in a single 12-lead electrocardiogram (ECG) test. While several trials have shown improved detection of AF with prolonged ECG monitoring, this strategy is associated with relatively high cost, labor intensity, and patient inconvenience, thereby making it challenging to routinely implement in all hospitals. Fortunately, conventional 24-h Holter monitoring and repeated 12-lead ECGs are readily available to detect paroxysmal AF in all hospitals, but is unclear which is the better strategy for evaluating undiagnosed AF. The objective of his study is to conduct a randomized trial of serial 12-lead ECGs vs. 24-hour Holter monitoring in the detection of AF in ischemic stroke patients without known AF. Methods and analysis: We plan to enroll 1200 participants from six hospitals in Taiwan. Patients will be eligible for enrollment if they are admitted for an acute ischemic stroke within 2 days, are ≥65 years of age, and have no known AF by history or on baseline ECG at admission. We will randomly assign participants in a 1:1 ratio to undergo daily 12-lead ECG once daily for 5 days (intervention group) or 24-h Holter monitoring (control group). Primary outcome is newly detected AF on a 12-lead ECG or AF lasting ≥30 s on Holter monitoring. Trial registration number: ClinicalTrials.gov Identifier: NCT02578979.

In Taiwan, the prevalence of hyperlipidemia increased due to lifestyle and dietary habit changes. Low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) are all significant predicting factors of coronary artery disease in Taiwan. We recognized that lipid control is especially important in patients with existed atherosclerotic cardiovascular diseases (ASCVD), including coronary artery disease (CAD), ischemic stroke and peripheral arterial disease (PAD). Because the risk of ASCVD is high in patients with diabetes mellitus (DM), chronic kidney disease (CKD) and familial hypercholesterolemia (FH), lipid control is also necessary in these patients. Lifestyle modification is the first step to control lipid. Weight reduction, regular physical exercise and limitation of alcohol intake all reduce triglyceride (TG) levels. Lipid-lowering drugs include HMG-CoA reductase inhibitors (statins), cholesterol absorption inhibitors (ezetimibe), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, nicotinic acids (niacin), fibric acids derivatives (fibrates), and long-chain omega-3 fatty acids. Statin is usually the first line therapy. Combination therapy with statin and other lipid-lowering agents may be considered in some clinical settings. For patients with acute coronary syndrome (ACS) and stable CAD, LDL-C < 70 mg/dL is the major target. A lower target of LDL-C 40 in men and >50 mg/dL in women in DM. LDL-C increased CV risk in patients with CKD. In adults with glomerular filtration rate (GFR) < 60 mL/min/1.73m2 without chronic dialysis (CKD stage 3–5), statin therapy should be initiated if LDL-C ≥ 100 mg/dL. Ezetimibe can be added to statin to consolidate the CV protection in CKD patients. Mutations in LDL receptor, apolipoprotein B and PCSK9 genes are the common causes of FH. Diagnosis of FH usually depends on family history, clinical history of premature CAD, physical findings of xanthoma or corneal arcus and high levels of LDL-C. In addition to conventional lipid lowering therapies, adjunctive treatment with mipomersen, lomitapide, or PCSK9 inhibitors become necessary to further reduce LDL-C in patients with FH. Overall, these recommendations are to help the health care professionals in Taiwan to treat hyperlipidemia with current scientific evidences. We hope the prescription rate of lipid lowering drugs and control rate of hyperlipidemia in high risk patients could be increased by implementation of the clinical guidelines. The major purpose is to improve clinical outcomes of these high risk patients through the control of hyperlipidemia.

We aim to evaluate the accuracy of the new prehospital notification criteria for patients with potential acute stroke in the prehospital setting. Methods: We conducted a retrospective observational study from March 2011 to February 2013 of potential acute stroke patients prenotified using the new criteria which were: (1) positive Cincinnati Prehospital Stroke Scale (CPSS); (2) symptom onset within 3 hours; and (3) blood glucose level > 60 mg/dL. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the new criteria were calculated and outcomes of acute stroke patients were reported. Data of all patients with stroke or transient ischemic attack (TIA) transported to the destination hospital were also obtained to evaluate the compliance of emergency medical technicians. Results: There were 2888 patients suspected of stroke by emergency medical technicians and 221 patients prenotified due to meeting the criteria. The PPV, NPV, sensitivity, and specificity of the new criteria were 76.9%, 96.6%, 64.9%, and 98.1%, respectively. Onset time > 3 hours (24/51, 47.1%) and seizure (27.5%) were the two most common conditions leading to false prenotification. Of all prenotified patients, 23.1% (51/221) received thrombolytic therapy. Hemorrhagic stroke or ischemic stroke with hemorrhagic transformation (53.8%) and minor symptoms or rapid recovery (26.9%) were the most common reasons excluding correctly prenotified patients from thrombolytic therapy. Conclusion: The accuracy of the new prehospital stroke criteria has higher PPV and specificity compared to previous CPSS validation studies.

Aggressive and persistent control of risk factors is recommended for prevention of secondary comorbidities in patients with cardiovascular diseases. This study aimed to evaluate guideline recommendations for achieving targets for lipid and blood pressure (BP) control in patients with cardiovascular diseases in Taiwan. Methods: This multicenter cohort study was conducted in 14 hospitals in Taiwan. A total of 3316 outpatients who had established cerebrovascular disease (CVD), coronary artery disease (CAD), or both were recruited. Risk factors for comorbid conditions such as high BP, sugar, hemoglobin A1C, abnormal lipids, lipoproteins, and medication use were compared between patients with CVD, CAD, or both. Results: Of all patients, 503 (15.2%) had CVD only, 2568 (77.4%) had CAD only, and 245 (7.4%) had both CVD and CAD. Compared with patients who had only CAD, those with CVD were older, had higher frequency of hypertension, and lower frequency of diabetes mellitus. Patients with CAD were more likely to receive lipid-lowering and antihypertensive drugs than those with CVD (p

Mannitol is commonly used in patients with increased intracranial pressure (ICP), but its effect on cerebrovascular pressure reactivity (CVPR) is uncertain. We analyzed the changes of pressure reactivity index (PRx) during the course of mannitol treatment. Methods: Twenty-one patients who received mannitol treatment for increased ICP were recruited prospectively. Continuous waveforms of arterial blood pressure (ABP) and ICP were collected simultaneously for 60 minutes (10 minutes at baseline and 50 minutes since mannitol administration) during 37 events of mannitol treatment. The correlation coefficients between the mean ABP and ICP were averaged every 10 minutes and labeled as the PRx. The linear correlation of six time points of PRx in each event was calculated to represent the trend of CVPR changes. The negative slope of correlation was defined as improvement in CVPR under mannitol treatment and vice versa. Results: At baseline, the average of ICP was 26.0 ± 9.1 mmHg and the values of PRx were significantly correlated with ICP (p = 0.0044, r = 0.46). After mannitol administration, the average of ICP decreased significantly to 21.2 ± 11.1 mmHg (p = 0.036), and CVPR improved in 59.4 % of all events. Further analysis showed that low baseline cerebral perfusion pressure was the only hemodynamic parameter significant association with the improvement of CVPR after mannitol treatment (p = 0.039). Conclusion: Despite lowering ICP, mannitol may have diverse effects on CVPR in patients with intracranial hypertension. Our study suggests that mannitol infusion may have a beneficial effect on CVPR, particularly in those with a low cerebral perfusion pressure at baseline.

Stroke is a leading cause of death and disability in industrialized countries. Approximately 8–14% of stroke survivors suffer from central post-stroke pain (CPSP) when hemorrhagic stroke occurs in lateral thalamic regions, which severely affects their quality of life. Because the mechanisms of CPSP are not well understood, effective treatments have not been developed. In the present study, we tested the hypothesis that persistent CPSP is caused by P2X7 receptor activation after brain tissue damage and subsequent elevations in inflammatory cytokines. A thalamic hemorrhagic rat model was used, characterized by thermal and mechanical allodynia that develops in the subacute to chronic phases upon CPSP onset. We found a significant increase in P2X7 expression in reactive microglia/macrophages in thalamic peri-lesion tissues at 5 weeks post-hemorrhage. Thalamic P2X7 receptors were directly involved in pain transmission and hypersensitivity. The systemic targeting of P2X7 receptors during the acute stage of hemorrhage rescued abnormal pain behaviors and neuronal activity in the thalamocingulate pathway by reducing reactive microglia/macrophage aggregation and associated inflammatory cytokines. After CPSP onset, the targeting of interleukin-1β reversed abnormal pain sensitivity. The aberrant spontaneous thalamocortical oscillations in rats with CPSP were modulated by blocking P2X7 receptors. Taken together, our results suggest that targeting P2X7 may be bi-effective in the treatment of CPSP, as both a pain blocker and immunosuppressant that inhibits inflammatory damage to brain tissue. P2X7 receptors may serve as a potential target to prevent the occurrence of CPSP and may be beneficial for the recovery of patients from stroke.

To determine whether utilization of emergency medical service (EMS) can increase use and expedite delivery of the thrombolytic therapy in acute ischemic stroke patients. Methods: We analyzed consecutive patients presenting to the emergency department (ED) with an ischemic stroke within 72 hours of symptom onset from a prospective stroke registry. Variables associated with early ED arrival (within 3 hours of stroke onset) and administration of intravenous thrombolytic therapy were analyzed. Results: From January 1, 2010 to July 31, 2011, there were 1081 patients (62.3% men, age 69.6 ± 13 years) included in this study. Among them, 289 (26.7%) arrived in the ED within 3 hours, and 88 (8.1%) received thrombolytic therapy. Patients who arrived at the ED by EMS (n = 279, 25.8%) were independently associated with earlier ED arrival (adjusted odds ratio = 3.68, 95% confidence interval = 2.54–5.33), and higher chance of receiving thrombolytic therapy (adjusted odds ratio = 3.89, 95% confidence interval = 1.86–8.17). Furthermore, utilization of EMS significantly decreased onset-to-needle time by 26 minutes in patients receiving thrombolytic therapy. Conclusion: Utilization of EMS can not only help acute ischemic stroke patients in early presentation to ED, but also effectively facilitate thrombolytic therapy and shorten the onset-to-needle time.

Intracranial dural arteriovenous fistulas (DAVFs) can be complicated by ischemic stroke. This study investigated the frequency and determinants of ischemic stroke in patients with intracranial DAVF. Methods: We conducted a retrospective study of consecutive patients with intracranial DAVF. Patients with pure hemorrhagic stroke or without available brain imaging for clarifying stroke type were excluded. DAVF was diagnosed by cerebral catheter angiography. Cognard classification and location of DAVFs were ascertained. The clinical characteristics, outcome, and radiographic findings were recorded. Factors associated with occurrence of ischemic stroke in the patients with DAVFs were determined. Results: A total of 134 patients were enrolled. Six patients (4.5%) had ischemic stroke (mean age: 53.8 ± 13.4 years) and 128 patients were free from stroke (mean age: 55.4 ± 15.2 years). Men accounted for 83% in the ischemic stroke group and 34% in the non-stroke group. Chemosis, exophthalmos and tinnitus were more frequent in the non-stroke group, whereas seizure and mental decline were more frequent in the ischemic stroke group. DAVF was associated with highest risk of ischemic stroke at locations other than the cavernous sinus or large sinuses. Ischemic stroke also correlated with types of DAVF involving cortical venous drainage, including type IIb (18%), III (15%), and IV (100%). No patient with DAVF type I and IIa had ischemic stroke. The rate of ischemic stroke in patients with concomitant DAVF and cerebral sinus thrombosis was higher than in DAVF patients without cerebral sinus thrombosis. Venous infarct was the major subtype of ischemic stroke in five DAVF patients. Endovascular therapy was the most common choice in both groups, and fewer patients in the ischemic stroke group did not receive any treatment for DAVFs. Conclusion: Location and type of DAVF were two important factors related to the occurrence of ischemic stroke in DAVF patients.

Studies of the safety and efficacy of drug-eluting stent (DES) implantation to treat vertebral artery (VA) ostial stenosis are lacking in the Asian population. The aim of this study was to evaluate the feasibility and safety of DES implantation to treat VA ostial stenosis in Asians. Methods: We retrospectively analyzed the medical and radiologic records of patients receiving VA origin stenting with DES from October 2004 to September 2006 in the National Taiwan University Hospital. Results: Eleven symptomatic patients (9 male; mean age, 72 years) with 11 lesions treated with DES were included. There were eight lesions treated with paclitaxel-eluting stents and three lesions treated with sirolimus-eluting stents. The success rate for implantation of a DES was 100%. The percentage of stenosis was significantly reduced after stenting (86 ± 5 to 2 ± 4%; p < 0.001). No peri-interventional neurologic, vascular, or other medical complications were noted. All patients were asymptomatic at the mean follow-up time of 18.7 ± 8.6 months (range, 6-30 months). Two patients received repeat angiography at 4 or 8 months after stenting. No significant in-stent restenosis was found. Conclusion: Symptomatic VA origin stenosis can be treated safely and effectively with DES in Asians.

High tissue matrix metalloproteinase (MMP) activity has been reported to be associated with atherosclerosis and plaque rupture. The aim of this study was to elucidate the diagnostic value of serum MMP-1 in carotid stenosis and its dynamic change after stenting. We measured high-sensitivity C-reactive protein (hs-CRP) and MMP-1 in 37 patients with carotid stenosis (≥ 50%) and 84 controls. In 30 patients who underwent stenting, MMP-1 and hs-CRP were assessed immediately after stenting. We found that patients with carotid stenosis exhibited significantly higher MMP-1 compared with controls, but there was no difference in hs-CRP. Moreover, MMP-1 was elevated immediately after stenting. In multivariate analyses, MMP-1 was negatively correlated with statin and angiotensin converting enzyme inhibitor/angiotensin-II receptor blocker use in controls. In conclusion, higher levels and rapid surge after stenting in patients with carotid stenosis indicate that MMP-1 is an important composition of plaques, and suggest its potential role in the assessment of plaque burden and stability of carotid stenosis.