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Ischemic heart disease (IHD) is a common and potentially lethal cardiovascular disorder. Coronary artery bypass grafting (CABG) is a standard procedure for treating IHD. This study aims to introduce a novel technique for proximal anastomoses in CABG. This clinical trial studied 29 cases and 29 matched controls. Data were gathered from June 2014 to June 2023. Regarding proximal anastomoses, the sequential partial aortic clamp was performed in cases, and the partial aortic clamp was done for controls. In the sequential partial aortic clamp technique, a relatively small or medium vascular clamp was used instead of one clamp for all proximal anastomoses, which closed a small amount of the aortic wall at each stage. At each stage, only one hole in the aortic wall and only one anastomosis between the conduit and the aorta was performed. After the end of each anastomosis, the clamp was opened and placed on another part of the aorta, and the next anastomosis was performed. CK-MB (p < 0.001, Eta Squared = 0.255) level was significantly lower in cases that underwent sequential partial ascending aorta clamping. However, cTnI level was not statistically different among cases and controls(p = 0.05). Of all patients, 3 (10.3%) cases and 12 (41.4%) controls developed with postoperative atrial fibrillation (p = 0.007). The sequential partial aortic clamp technique leads to less myocardial injury than the partial aortic clamp technique. Also, patients undergoing sequential partial aortic clamp technique are less likely to develop postoperative atrial fibrillation. [ABSTRACT FROM AUTHOR]

LT3001 is a novel synthetic small molecule with thrombolytic and free radical scavenging activities. In this study, we tested the effects of LT3001 as a potential alternative thrombolytic in focal embolic ischemic stroke rat model. Stroked rats received intravenous injection of 10 mg/kg LT3001 or tPA at 1.5, 3, or 4.5 h after stroke, respectively, and the outcomes were measured at different time points after stroke by performing multi-parametric MRI, 2,3,5-triphenyltetrazolium chloride (TTC) staining, and modified neurological severity score. Lastly, we assessed the effect of LT3001 on the tPA activity in vitro, the international normalized ratio (INR), and the serum levels of active tPA and plasminogen activator inhibitor-1 (PAI-1). LT3001 treated at 1.5 h after stroke is neuroprotective by reducing the CBF lesion size and lowering diffusion and T2 lesion size measured by MRI, which is consistent with the reduction in TTC-stained infarction. When treated at 3 h after stroke, LT3001 had significantly better therapeutic effects regarding reduction of infarct size, swelling rate, and hemorrhagic transformation compared to tPA. When treated at 4.5 h after stroke, tPA, but not LT3001, significantly increased brain swelling and intracerebral hemorrhagic transformation. Lastly, LT3001 did not interfere with tPA activity in vitro, or significantly alter the INR and serum levels of active tPA and PAI-1 in vivo. Our data suggests that LT3001 is neuroprotective in focal embolic stroke rat model. It might have thrombolytic property, not interfere with tPA/PAI-1 activity, and cause less risk of hemorrhagic transformation compared to the conventional tPA. Taken together, LT3001 might be developed as a novel therapy for treating thrombotic ischemic stroke. [ABSTRACT FROM AUTHOR]

Objective: The scope of this paper is to review the subtypes of transient ischemic attack (TIA) and minor stroke (mS) in which a surgical treatment is needed, discussing the importance and the timing of a multidisciplinary approach, in order to achieve an optimized management and prevent major strokes or other critical complications. Materials and methods: The keywords "transient ischemic attack," "minor stroke," "surgical treatment," "vascular surgery," "heart surgery," "neurosurgery," and "multidisciplinary" were searched using MEDLINE, EMBASE, and Scopus. Relevant search results were discussed by the authors for references inclusion. Results: Notwithstanding that best medical therapy is usually the first choice for the most part of cases, there are specific but recurrent etiologies that must be properly recognized because of a potential surgical approach, even in urgency. In fact, symptomatic carotid stenosis, or particular cases of hemodynamic cerebrovascular events, should be promptly referred to vascular surgeon, since increasing evidences highlighted a benefit from an early artery revascularization. In addition, beyond arrhythmic causes, cardioembolic events due to bacterial endocarditis and atrial myxoma should be quickly diagnosed, possibly in emergency department, because they are a presumptive urgency for heart surgery. In addition to the above-mentioned conditions, in patients suffering from vertebrobasilar TIA or mS, clinicians should keep in mind the Bow Hunter disease, because surgical artery decompression can represent the only suitable treatment in selected cases. Conclusions: TIA and mS require a multidisciplinary in order to discuss therapeutic options, comparing risks and benefits and determining the best timing for an optimized management. [ABSTRACT FROM AUTHOR]

Background: Embolism as a cause of stroke is widely neglected in Moyamoya angiopathy (MMA), and recommendations for use of antiplatelet therapy (APT) vary. We examined the presence of microembolic signals (MES) during transcranial Doppler (TCD) monitoring and assessed the effects of APT on the occurrence of MES in MMA. Patients and methods: We retrospectively analysed patients with MMA treated at our centre between 2011 and 2021. TCD was performed at first presentation and at most visits, while number of visits varied between individual patients. TCD was performed for 30 min bilaterally. Patient demographics, vascular risk factors, and antiplatelet treatment were collected from each clinic visit and ischemic and haemorrhagic episodes were captured as recorded during follow-up visits. Results: 209 patients were included in the analysis (mean age 38.7 ± 15.3, 28% male). 21 patients with 27 MES-positive TCD examinations were identified (10%). Patient characteristics were similar in MES-positive and MES-negative groups. However, recent ischemic events were detected at a significantly higher rate in MES-positive patients (42.9% vs 4.8%, p < 0.001). After MES detection, change of antiplatelet drug regime was performed, leading to loss of MES in all cases. Dual APT was preferably used in the MES-positive group (p < 0.001) but no significant difference of haemorrhage during follow-up-visits was observed. Reduction of APT before bypass-surgery triggered MES in four patients. Conclusion: APT is required in patients with MMA. MES monitoring may help to identify risk patients in need of intensified APT. [ABSTRACT FROM AUTHOR]

The aim of the study was to find markers of high-risk cardioembolic etiology (HRCE) in patients with cryptogenic strokes (CS) through the analysis of intracranial clot by flow cytometry (FC). A prospective single-center study was designed including patients with large vessel occlusion strokes. The percentage of granulocytes, monocytes, lymphocytes, and monocyte-to-lymphocyte ratio (MLr) were analyzed in clots extracted after endovascular treatment (EVT) and in peripheral blood. Large arterial atherosclerosis (LAA) strokes and high-risk cardioembolic (HRCE) strokes were matched by demographics and acute reperfusion treatment data to obtain FC predictors for HRCE. Multilevel decision tree with boosting random forest classifiers was performed with each feature importance for HRCE diagnosis among CS. We tested the validity of the best FC predictor in a cohort of CS that underwent extensive diagnostic workup. Among 211 patients, 178 cases underwent per-protocol workup. The percentage of monocytes (OR 1.06, 95% CI 1.01–1.11) and MLr (OR 1.83, 95% CI 1.12–2.98) independently predicted HRCE diagnosis when LAA clots (n = 28) were matched with HRCE clots (n = 28). Among CS (n = 82), MLr was the feature with the highest weighted importance in the multilevel decision tree as a predictor for HRCE. MLr cutoff point of 1.59 yield sensitivity of 91.23%, specificity of 44%, positive predictive value of 78.79%, and negative predictive value of 68.75 for HRCE diagnosis among CS. MLr ≥ 1.6 in clot analysis predicted HRCE diagnosis (OR, 6.63, 95% CI 1.85–23.71) in a multivariate model adjusted for age. Clot analysis by FC revealed high levels of monocyte-to-lymphocyte ratio as an independent marker of cardioembolic etiology in cryptogenic strokes. [ABSTRACT FROM AUTHOR]

Purpose of Review: The initial ESUS construct presumed that atrial fibrillation (AF) would be detected in a substantial percentage of patients, but subsequent studies have determined that the rate of AF detection is much lower than anticipated, thereby highlighting other potential causes of ESUS. To date, there is no clear consensus supporting PFO closure or anticoagulation in ESUS patients. In this review, we discuss the recent studies on potential causes of ESUS and related work-up as well as report the recent trials on the treatment of ESUS. Recent Findings: Some of the potential causes of ESUS are undetected AF, patient foramen ovale (PFO), ipsilateral non-stenotic carotid plaques, carotid webs, and underlying malignancies. Other emerging rare causes of ESUS include pulmonary arteriovenous malformations (PAVM), cavernous carotid aneurysms, and intracranial arterial aneurysms. Recently, the American Academy of Neurology published a shared decision-making approach between neurologists and cardiologists outlining what should be done regarding PFO closure. Most recent clinical trials including ATTICUS (apixaban for treatment of embolic stroke of undetermined source) suggest that the strategy of empiric anticoagulation may not be the most appropriate way to manage patients with ESUS. Summary: The negative results of the trials could reflect that many cases of ESUS are perhaps due to embolism from nonstenosing atherosclerotic lesions, where anticoagulation has not been shown to be beneficial. Incorporating markers of atrial cardiopathy may still prove useful in identifying ESUS patients in whom anticoagulation is superior to antiplatelet therapy for secondary stroke prevention. Therefore, the results of the ongoing ARCADIA trial are therefore eagerly awaited. [ABSTRACT FROM AUTHOR]

Introduction: The latest research in ischaemic stroke pathogenesis is directed to unveil what is inside embolic stroke of undetermined source (ESUS). Whether vulnerable non stenotic carotid plaques (NSTEPS), i.e. atherosclerotic lesions in carotid arteries determining a stenosis lower than 50%, may represent a cause of stroke in ESUS is a matter of debate. We aimed to study the prevalence of NSTEPS in an ESUS population.We retrospectively identified a consecutive ESUS population admitted to the Stroke-Unit of Careggi Hospital, Italy from 2019 to 2022. Characteristics of atherosclerotic plaques (thickness, ulceration, hypodensity) and their location (ipsilateral versus contralateral to the stroke) were studied on carotid CT angiography (CTA). Follow-up data were recorded up to 24 months after stroke.We identified 57 ESUS patients with unilateral ischaemic lesions studied with CTA; 53 (93%) had an ipsilateral carotid plaque, 81% contralateral, (p = 0.754) and 74% both. Plaques ipsilateral to stroke were ≥ 3 mm thick in 15 (28%) patients; hypodense in 14 (26%) and ulcerated in 5 (9%). The frequency of hypodensity was higher in ipsilateral compared to contralateral plaques (26% vs. 13%, p = 0.039) and ulceration was around four times more frequent, although not statistically significant (9% vs. 2%, p = 0.219). At follow-up, six patients had stroke recurrence (11%), 2 of them were in the same vascular territory of the former.Our data suggest that plaques ipsilateral to stroke seem to be more frequently vulnerable and consequently more prone to embolization. Prospective data are needed to clarify the causal role of NSTEPS in ESUS.Patients and methods: The latest research in ischaemic stroke pathogenesis is directed to unveil what is inside embolic stroke of undetermined source (ESUS). Whether vulnerable non stenotic carotid plaques (NSTEPS), i.e. atherosclerotic lesions in carotid arteries determining a stenosis lower than 50%, may represent a cause of stroke in ESUS is a matter of debate. We aimed to study the prevalence of NSTEPS in an ESUS population.We retrospectively identified a consecutive ESUS population admitted to the Stroke-Unit of Careggi Hospital, Italy from 2019 to 2022. Characteristics of atherosclerotic plaques (thickness, ulceration, hypodensity) and their location (ipsilateral versus contralateral to the stroke) were studied on carotid CT angiography (CTA). Follow-up data were recorded up to 24 months after stroke.We identified 57 ESUS patients with unilateral ischaemic lesions studied with CTA; 53 (93%) had an ipsilateral carotid plaque, 81% contralateral, (p = 0.754) and 74% both. Plaques ipsilateral to stroke were ≥ 3 mm thick in 15 (28%) patients; hypodense in 14 (26%) and ulcerated in 5 (9%). The frequency of hypodensity was higher in ipsilateral compared to contralateral plaques (26% vs. 13%, p = 0.039) and ulceration was around four times more frequent, although not statistically significant (9% vs. 2%, p = 0.219). At follow-up, six patients had stroke recurrence (11%), 2 of them were in the same vascular territory of the former.Our data suggest that plaques ipsilateral to stroke seem to be more frequently vulnerable and consequently more prone to embolization. Prospective data are needed to clarify the causal role of NSTEPS in ESUS.Results: The latest research in ischaemic stroke pathogenesis is directed to unveil what is inside embolic stroke of undetermined source (ESUS). Whether vulnerable non stenotic carotid plaques (NSTEPS), i.e. atherosclerotic lesions in carotid arteries determining a stenosis lower than 50%, may represent a cause of stroke in ESUS is a matter of debate. We aimed to study the prevalence of NSTEPS in an ESUS population.We retrospectively identified a consecutive ESUS population admitted to the Stroke-Unit of Careggi Hospital, Italy from 2019 to 2022. Characteristics of atherosclerotic plaques (thickness, ulceration, hypodensity) and their location (ipsilateral versus contralateral to the stroke) were studied on carotid CT angiography (CTA). Follow-up data were recorded up to 24 months after stroke.We identified 57 ESUS patients with unilateral ischaemic lesions studied with CTA; 53 (93%) had an ipsilateral carotid plaque, 81% contralateral, (p = 0.754) and 74% both. Plaques ipsilateral to stroke were ≥ 3 mm thick in 15 (28%) patients; hypodense in 14 (26%) and ulcerated in 5 (9%). The frequency of hypodensity was higher in ipsilateral compared to contralateral plaques (26% vs. 13%, p = 0.039) and ulceration was around four times more frequent, although not statistically significant (9% vs. 2%, p = 0.219). At follow-up, six patients had stroke recurrence (11%), 2 of them were in the same vascular territory of the former.Our data suggest that plaques ipsilateral to stroke seem to be more frequently vulnerable and consequently more prone to embolization. Prospective data are needed to clarify the causal role of NSTEPS in ESUS.Discussion and conclusions: The latest research in ischaemic stroke pathogenesis is directed to unveil what is inside embolic stroke of undetermined source (ESUS). Whether vulnerable non stenotic carotid plaques (NSTEPS), i.e. atherosclerotic lesions in carotid arteries determining a stenosis lower than 50%, may represent a cause of stroke in ESUS is a matter of debate. We aimed to study the prevalence of NSTEPS in an ESUS population.We retrospectively identified a consecutive ESUS population admitted to the Stroke-Unit of Careggi Hospital, Italy from 2019 to 2022. Characteristics of atherosclerotic plaques (thickness, ulceration, hypodensity) and their location (ipsilateral versus contralateral to the stroke) were studied on carotid CT angiography (CTA). Follow-up data were recorded up to 24 months after stroke.We identified 57 ESUS patients with unilateral ischaemic lesions studied with CTA; 53 (93%) had an ipsilateral carotid plaque, 81% contralateral, (p = 0.754) and 74% both. Plaques ipsilateral to stroke were ≥ 3 mm thick in 15 (28%) patients; hypodense in 14 (26%) and ulcerated in 5 (9%). The frequency of hypodensity was higher in ipsilateral compared to contralateral plaques (26% vs. 13%, p = 0.039) and ulceration was around four times more frequent, although not statistically significant (9% vs. 2%, p = 0.219). At follow-up, six patients had stroke recurrence (11%), 2 of them were in the same vascular territory of the former.Our data suggest that plaques ipsilateral to stroke seem to be more frequently vulnerable and consequently more prone to embolization. Prospective data are needed to clarify the causal role of NSTEPS in ESUS. [ABSTRACT FROM AUTHOR]

Background: Abdominal aortic aneurysms (AAA) can present asymptomatically and may be found through routine screening or seen incidentally on imaging. Rupture due to weaking of the aortic wall is the main complication of an AAA and leads to approximately 200,000 deaths annually worldwide. Clinically, AAA rupture most frequently presents with abdominal and/or back pain, pulsatile abdominal mass, and hypotension. Here, we present an unusual presentation of embolic cerebrovascular accident associated with an AAA rupture. Case presentation: A 58-year-old African American man transported to the emergency department via ambulance presents with altered mental status and unilateral extremity weakness. The initial presentation was concerning for acute cerebrovascular accident, acute kidney injury, severe sepsis, and urinary tract infection. Several hours after the initial presentation, the patient's abdomen began to appear distended and he became hypotensive. An abdominal CT was ordered which showed a large AAA rupture with a retroperitoneal bleed. The patient was transferred to a higher-level medical center for surgical repair. Conclusion: Abdominal aortic aneurysm rupture can rarely present due to an acute cerebrovascular accident with altered mental status and focal neurologic deficits. [ABSTRACT FROM AUTHOR]

Background: Patients with atrial fibrillation (AF) who are on long-term direct oral anticoagulants (DOAC) with low anti-Xa or anti-IIa levels may be at higher risk of recurrent stroke. However, no prospective post-marketing study has investigated these DOAC plasma levels at the time of embolic stroke. The aim of this study was to assess the anti-Xa (rivaroxaban, apixaban) and anti-IIa (dabigatran) plasma levels in DOAC-treated AF patients at the time of acute embolic stroke. Patients and methods: We prospectively identified 43 patients with AF on long-term DOAC who experienced embolic strokes. We compared the DOAC plasma levels of these patients with a control sample of 57 patients who tolerated long-term therapeutic dose DOAC therapy without any adverse event. DOAC levels were assessed with drug-specific anti-Xa chromogenic analysis (rivaroxaban, apixaban) and with Hemoclot Thrombin Inhibitor assay (dabigatran). Results: Dabigatran-treated patients with stroke had significantly lower anti-IIa levels when compared with the trough (40.7 ± 36.9 vs. 85.4 ± 57.2 ng/mL, p < 0.05) and peak samples of the controls (40.7 ± 36.9 vs. 138.8 ± 78.7 ng/mL, p < 0.001). Similarly, there were significantly lower anti-Xa levels in apixaban-treated patients with stroke compared to the trough control samples (72.4 ± 46.7 vs. 119.9 ± 81.7 ng/mL, p < 0.05), and in rivaroxaban- and apixaban-treated patients when compared to peak control samples (rivaroxaban: 42.7 ± 31.9 vs. 177.6 ± 38.6 ng/mL, p < 0.001; apixaban: 72.4 ± 46.7 vs. 210.9 ± 88.7 ng/mL, p < 0.001). Conclusion: This observational study showed significantly lower anti-IIa and anti-Xa plasma levels in AF patients with embolic stroke compared to those who tolerated long-term therapeutic dose DOAC therapy. [ABSTRACT FROM AUTHOR]

Background and purpose: Multiple embolic sources are sometimes observed simultaneously in patients with embolic stroke. The present study investigated the effects of coexisting aortic arch atheroma ≥ 4 mm thick and atrial fibrillation (AF) on short-term stroke recurrence and functional outcome. Methods: Transesophageal echocardiography (TEE) was performed in consecutive embolic stroke patients, and 395 patients were classified into 4 groups according to the presence of aortic arch atheroma ≥ 4 mm thick and AF: AF − /ARCH − group, AF + /ARCH − group, AF − /ARCH + group, and AF + /ARCH + group. In accordance with these 4 groups, we evaluated stroke recurrence and all-cause death for 3 months after stroke onset, and also evaluated the 3-month functional outcome using the modified Rankin scale (mRS). Results: Among the 128 AF patients, 39.1% also had aortic arch atheroma ≥ 4 mm thick. Of the 395 enrolled cases, the AF + /ARCH + group showed the highest frequencies of stroke recurrence and all-cause death during 3 months after onset. On multivariate analysis, stroke recurrence or all-cause death during 3 months after onset was relatively more frequent in the AF + /ARCH + group than in the AF + /ARCH − group (OR, 2.34; 95% CI, 0.82–6.69; p = 0.11), but that was not statistically significant, and poor functional outcome (mRS score 3–6) at 3 months was significantly more frequent in the AF + /ARCH + group than in the AF + /ARCH − group (OR, 2.59; 95% CI, 1.08–6.24; p = 0.0339). Conclusions: Aortic arch atheroma concomitant with AF is not rare and appears associated with increased risks of stroke recurrence and poor functional outcome. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation and flutter are well-known causes of stroke. Whether other atrial arrhythmias categorized as paroxysmal supraventricular tachycardia (PSVT) are associated with stroke is less clear. We aimed to evaluate the association of PSVT with ischemic and embolic stroke and its impact on short-term outcomes in hospitalized stroke patients.Methods: National Inpatient Sample database of the USA was used to assess the association of PSVT with ischemic stroke. Atrial fibrillation and flutter were excluded to minimize the confounding effects. The association of PSVT with stroke was evaluated using univariate and multivariate analysis. Subgroup analyses by gender, age, and stroke type were also performed.Results: PSVT was associated with increased odds of overall ischemic stroke in univariate [OR 1.18 (95% CI 1.09-1.27) p < 0.001] analysis. No such association was observed in multivariate analysis (OR 1.06 (95% CI 0.98-1.14) p = 0.1) or with subgroup analysis by gender and age. However, PSVT was associated with embolic stroke in both univariate (OR 2.01 (95%CI 1.67-2.43, p < 0.001) and multivariate analysis (OR 1.7 (95%CI 1.4-2.14) p < 0.001) as well as in subgroup analyses by gender and age. Furthermore, the presence of PSVT was associated with increased mortality in embolic stroke (OR 4.11, CI 2.29 to 7.39, p < 0.001) and increased total hospital cost and length of hospital stay in all stroke types.Conclusions: PSVT is independently associated with higher prevalence of embolic stroke but not with overall ischemic stroke. Patients with embolic stroke in the presence of PSVT have worse in-hospital outcomes with increased mortality. [ABSTRACT FROM AUTHOR]

Purpose: Lacunar infarcts are thought to result from occlusion of small penetrating arteries due to microatheroma and lipohyalinosis, pathognomonic for cerebral small vessel disease (CSVD). Concurrent embolic ischemic lesions indicate a different stroke mechanism. The purpose of this study was to examine the clinical characteristics and outcome of patients with lacunar infarcts and concurrent embolic infarcts on diffusion-weighted imaging (DWI). Methods: All patients screened for the WAKE-UP trial (ClinicalTrials.gov number, NCT01525290) were reviewed for acute lacunar infarcts and concurrent embolic lesions on baseline DWI. Clinical characteristics and outcome were compared between lacunar infarct patients with and without concurrent embolic lesions. Results: Of 244 patients with an acute lacunar infarct, 20 (8.2%) had concurrent acute embolic infarcts. Compared to patients with a lacunar infarct only, patients with concurrent embolic infarcts were older (mean age 69 years vs. 63 years; p = 0.031), more severely affected (median National Institutes of Health Stroke Scale [NIHSS] score 5 vs. 4; p = 0.046), and—among those randomized—had worse functional outcome at 90 days (median modified Rankin Scale [mRS] 3 vs. 1; p = 0.011). Conclusion: Approximately 8% of lacunar infarct patients show concurrent embolic lesions suggesting a stroke etiology other than CSVD. These patients are more severely affected and have a worse functional outcome illustrating the need for a thorough diagnostic work-up of possible embolic sources even in patients with an imaging-defined diagnosis of lacunar infarcts. [ABSTRACT FROM AUTHOR]

Purpose of review: Cryptogenic stroke describes a subset of ischemic stroke for which no cause can be found despite a structured investigation. There are a number of putative mechanisms of cryptogenic ischemic stroke including a covert structural cardiac lesion, paroxysmal atrial fibrillation, hypercoagulable state or undiagnosed malignancy. Because many of these proposed mechanisms are embolic – and based on studies of thrombus history showing commonalities between thrombus composition between cardioembolic and cryptogenic strokes – the concept of embolic stroke of undetermined source (ESUS) (Hart et al. Lancet Neurol. 13(4):429–38, 2014; Stroke. 48(4):867–72, 2017) has been proposed to describe cryptogenic strokes that may warrant systemic anticoagulation. In this review, we discuss the phenomena of cryptogenic stroke, ESUS and a proposed management pathway. Recent findings: 1. The concept of ESUS was proposed in 2014 as a potentially useful therapeutic entity. Two recent trials – NAVIGATE-ESUS (Hart et al. N Engl J Med. 378(23):2191–201, 2018) and RESPECT-ESUS (Diener 2018) were proposed based on this concept. They were negative for their primary endpoint and for the secondary endpoint of ischemic stroke recurrence. Post-hoc analysis of the WARSS trial (Longstreth et al. Stroke. 44(3):714–9, 2013) suggested that people with elevated pro-BNP benefited from systemic anticoagulation whereas those with a normal pro-BNP did not. This led to the hypothesis that a subgroup of patients at higher risk for embolism from the left atrium would benefit from anticoagulation, even if the WARSS trial was negative for the primary endpoint. Thus, the ARCADIA trial (Kamel et al. Int J Stroke. 14(2):207–14, 2019) was proposed – a randomized, active-control, multi-center trial comparing apixaban with aspirin for secondary stroke prevention in patients with ESUS and biomarkers of left atrial cardiopathy. This trial is actively recruiting. 2. Carotid web – an intimal form of fibromuscular dysplasia – has come to increased prominence in the literature as a cause of embolic stroke. It is a non-stenosis, non-atherosclerotic lesion in the posterior wall of the internal carotid artery that leads to pooling with stasis of blood distal to the lesion and, as a consequence, embolic stroke. It is not usually detected by a standard stroke workup as it masquerades as non-calcified atherosclerosis and does not cause hemodynamically significant stenosis. There have been two major recent papers – a meta-analysis in Stroke (Zhang et al. Stroke. 49(12):2872–6, 2018) and narrative review in JAMA Neurology (Kim et al. JAMA Neurol. 2018) – that addressed this topic. Summary: Cryptogenic stroke describes a stroke for which no cause has been found. ESUS is a more precisely-defined entity that mandates a specific workup and implicates remote embolism as a cause of stroke. In ESUS, the options for further investigation include long-term cardiac monitoring, transesophageal echocardiography, investigation for occult malignancy or arterial hypercoagulability. Options for management include anti-platelet therapy (the current standard of care), empiric anticoagulation or enrollment in to a clinical trial examining the use of NOACs compared with aspirin for secondary prevention (such as ARCADIA or ATTICUS). In a person less than 60 years old with ESUS and a patent foramen ovale the risk of a recurrent stroke is low but recent trials have suggested that percutaneous device closure reduces this risk further with an acceptable complication rate. [ABSTRACT FROM AUTHOR]

Purpose: Reports from 3-T vessel wall MRI imaging have shown contrast enhancement following thrombectomy for acute stroke, suggesting potential intimal damage. Comparisons have shown higher SNR and more lesions detected by vessel wall imaging when using 7 T compared with 3 T. The aim of this study was to investigate the vessel walls after stent retriever thrombectomy using high-resolution vessel wall imaging at 7 T. Methods: Seven patients with acute stroke caused by occlusion of the distal internal carotid artery (T-occlusion), or proximal medial cerebral artery, and treated by stent retriever thrombectomy with complete recanalization were included and examined by 7-T MRI within 2 days. The MRI protocol included a high-resolution black blood sequence with prospective motion correction (iMOCO), acquired before and after contrast injection. Flow measurements were performed in the treated and untreated M1 segments. Results: All subjects completed the MRI examination. Image quality was independently rated as excellent by two neuroradiologists for all cases, and the level of motion artifacts did not impair diagnostic quality, despite severe motion in some cases. Contrast enhancement correlated with the deployment location of the stent retrievers. Flow data showed complete restoration of flow after treatment. Conclusion: Vessel wall imaging with prospective motion correction can be performed in patients following thrombectomy with excellent imaging quality at 7 T. We show that vessel wall contrast enhancement is the normal post-operative state and corresponds to the deployment location of the stent retriever. [ABSTRACT FROM AUTHOR]

Purpose: To examine the prevalence of the so-called bovine aortic arch variation (common origin of the brachiocephalic trunk and the left common carotid artery) in embolic stroke patients, compared with a control group. Methods: Aortic arch branching patterns were retrospectively evaluated in 474 individuals with (n = 152) and without (n = 322) acute embolic stroke of the anterior circulation. Contrast-enhanced CT scans of the chest and neck (arterial contrast phase, 1–2-mm slice thickness) were used to evaluate aortic arch anatomy. The stroke cohort included 152 patients who were treated for embolic strokes of the anterior circulation between 2008 and 2018. A total of 322 randomly selected patients who had received thoracic CT angiographies within the same time frame were included as a control group. Results: With a prevalence of 25.7%, the bovine aortic arch variant was significantly more common among patients suffering from embolic strokes, compared with 17.1% of control patients (p = 0.039, OR = 1.67, 95%CI = 1.05–1.97). Stroke patients were more likely to show the bovine arch subtype B (left common carotid artery originating from the brachiocephalic trunk instead of the aortic arch) (10.5% vs. 5.0%, p = 0.039, OR = 2.25, 95%CI = 1.09–4.63), while subtype A (V-shaped common aortic origin of the brachiocephalic trunk and the left carotid) was similarly common in both groups. There was no significant difference regarding the frequency of other commonly observed variant branching patterns of the aortic arch. Conclusion: The bovine aortic arch, particularly the bovine arch subtype B, was significantly more common among embolic stroke patients. This might be due to altered hemodynamic properties within the bovine arch. [ABSTRACT FROM AUTHOR]

Purpose: Determine whether the CHA2DS2-VASc score predicts rates of hospitalization associated with thromboembolic complications (TEC) in the 30, 60, and 90 days following cardioversion (CV) for atrial fibrillation (AF).Methods: The 2014 National Readmissions Database was analyzed to identify readmissions following the index hospitalization for AF and CV. A CHA2DS2-VASc score was calculated for each patient from diagnosis codes associated with the index admission. The primary outcome was the incidence of readmission due to TEC in the 30, 60, and 90 days after CV stratified by CHA2DS2-VASc scores ≤ 1, 2-3, and ≥ 4; the secondary outcome was specific clinical risk factors independently associated with TEC within 30 days of CV.Results: A total of 109,420 weighted index admissions for AF and CV were identified in between January 1, 2014, and November 30, 2014. Of these, 16,535 (15.1%) had a CHA2DS2-VASc score of 0-1, 39,544 (36.1%) had a score of 2-3, and 53,340 (48.8%) had a score of ≥ 4. Readmission due to TEC occurred in 48 (0.29%), 167 (0.42%), and 394 (0.74%) patients with CHA2DS2-VASc scores ≤ 1, 2-3, and ≥ 4, respectively, in the 90-day period after CV. The only significant predictor for 30-day TEC-associated readmission after CV was age > 65 years old.Conclusions: This study demonstrated the utility of CHA2DS2-VASc score in predicting TEC-associated readmission rate following CV and the temporal relationship of TEC to CV. Patients > 65 years old without other comorbidities may benefit from 30-day OAC following successful CV irrespective of the duration of AF episodes. [ABSTRACT FROM AUTHOR]

Purpose: The characterization of atherosclerotic carotid plaque plays a key role in the identification of patients at risk. The aim of our work was to evaluate the potentialities of carotid computed tomography angiography (CCTA) in assessing composition of atherosclerotic plaque. Materials and methods: We retrospectively evaluated 29 patients (7 women and 22 men, age range 54–81; mean age 69) who underwent carotid endarterectomy. All patients underwent pre-surgical CCTA using a 320-slice scanner. Post-processing reconstructions and analysis were performed using a specific software. Percentage of three different components of the atherosclerotic plaque (adipose, fibrotic and calcific) were classified based on Hounsfield unit values. Post-processing results were compared with histological analysis. Vessel and plaque parameters were compared using the Pearson correlation coefficient (r). Bland–Altman plots with 95% confidence intervals were calculated for correlation. McNemar's test was used for comparison of dichotomous variables. Results: A significant correlation between histology and CCTA was found with respect to the areas corresponding to adipose, fibrotic and calcified plaques. The existence of proportional bias was observed between the two quantifying methods with lower discrepancies found for the adipose and fibrotic plaque areas. The Bland–Altman analyses showed a mean bias of 3.2%, 2.5% and 0.6% between histology and CCTA, for adipose, fibrotic and calcified plaque areas, respectively. Conclusions: Multi-detector CT angiography represents a valuable technique to assess quantitatively the composition of atherosclerotic plaques, with particular reference to the prevalence of fibrotic tissue, and is a useful diagnostic tool to improve risk stratification of patients for cerebral stroke. [ABSTRACT FROM AUTHOR]

Tissue plasminogen activator (t-PA) is the only FDA-approved drug for acute ischemic stroke but poses risk for hemorrhagic transformation (HT). Cell therapy has been investigated as a potential therapy to improve recovery after stroke by the modulation of inflammatory responses and the improvement of blood-brain barrier (BBB) integrity, both of which are associated with HT after t-PA. In our present study, we studied the effect of autologous bone marrow mononuclear cells (MNCs) in an embolic stroke model. We administered MNCs in a rat embolic stroke 2 h after administering t-PA. We observed that even though autologous MNCs did not alter the incidence of HT, they decreased the severity of HT and reduced BBB permeability. One possible mechanism could be through the inhibition of MMP3 released by astrocytes via JAK/STAT pathway as shown by our in vitro cell interaction studies. [ABSTRACT FROM AUTHOR]

Cerebral tissue oxygenation (oxygen tension, pO) is a critical parameter that is closely linked to brain metabolism, function, and pathophysiology. In this work, we have used electron paramagnetic resonance oximetry with a deep-tissue multi-site oxygen-sensing probe, called implantable resonator, to monitor temporal changes in cerebral pO simultaneously at four sites in a rabbit model of ischemic stroke induced by embolic clot. The pO values in healthy brain were not significantly different among the four sites measured over a period of 4 weeks. During exposure to 15% O (hypoxia), a sudden and significant decrease in pO was observed in all four sites. On the other hand, brief exposure to breathing carbogen gas (95% O + 5% CO) showed a significant increase in the cerebral pO from baseline value. During ischemic stroke, induced by embolic clot in the left brain, a significant decline in the pO of the left cortex (ischemic core) was observed without any change in the contralateral sites. While the pO in the non-infarct regions returned to baseline at 24-h post-stroke, pO in the infarct core was consistently lower compared to the baseline and other regions of the brain. The results demonstrated that electron paramagnetic resonance oximetry with the implantable resonator can repeatedly and simultaneously report temporal changes in cerebral pO at multiple sites. This oximetry approach can be used to develop interventions to rescue hypoxic/ischemic tissue by modulating cerebral pO during hypoxic and stroke injury. [ABSTRACT FROM AUTHOR]

Previous studies showed recombinant annexin A2 (rA2) in combination with low-dose tissue-type plasminogen activator (tPA) improved thrombolytic efficacy and long-term neurological outcomes after embolic focal ischemia in rats. The objective of this study was to investigate the effects and mechanisms of the combination in early BBB integrity and cerebrovascular patency in the rat focal embolic stroke model. Ischemic brain infarct volume and hemorrhagic transformation were quantified at 24 h after stroke. At an earlier time point, 16 h after stroke, BBB integrity was evaluated by IgG extravasation, and the involved mechanisms were assessed for tight junction ZO-1 and adhesion junction ve-cadherin protein expression, matrix metalloproteinase activation, extracellular matrix collagen IV and endothelial barrier antigen expression, and activation of microglia/macrophages and astrocytes. While at the same time point, cerebrovascular patency was assessed by intravascular fibrin and platelet depositions. At 24 h after stroke, the combination showed significant reduction in brain infarction and intracerebral hemorrhage. At 16 h after stroke onset, the combination therapy significantly reduced BBB disruption, and improved preservation of the junction proteins ZO-1 and ve-cadherin, decreased activation of matrix metalloproteinase, inhibited degradation of extracellular matrix collagen IV and endothelial barrier antigen, and reduced microglia/macrophage and astrocytes activations. Meanwhile, the combination also significantly improved cerebrovascular patency by reducing intravascular fibrin and platelet depositions in the peri-infarct brain tissues. These results suggest the beneficial effects of the rA2 plus low-dose tPA combination may be mediated in part by the amelioration of BBB disruption and improvement of cerebrovascular patency. [ABSTRACT FROM AUTHOR]

Tissue plasminogen activator (tPA) is currently used in combination with endovascular procedures to enhance recanalization and cerebral reperfusion and is also currently administered as standard-of-care thrombolytic therapy to patients within 3-4.5 h of an ischemic stroke. Since tPA is not neuroprotective or cytoprotective, adjuvant therapy with a neuroprotective or an optimized cytoprotective compound is required to provide the best care to stroke victims to maximally promote clinical recovery. In this article, we describe the use of a sensitive standardized protease assay with CHSO-D-hexahydrotyrosine-Gly-Arg-p-nitroanilide•AcOH, a chromogenic protease substrate that is cleaved to 4-nitroaniline (p-nitroaniline) and measured spectrophotometrically at 405 nm (OD), and how the assay can be used as an effective screening assay to study drug-tPA interactions. While we focus on two compounds of interest in our drug development pipeline, the assay is broadly applicable to all small molecule neuroprotective or cytoprotective compounds currently being discovered and developed worldwide. In this present study, we found that the specific tPA inhibitor, plasminogen activator inhibitor-1 (PAI-1; 0.25 μM), significantly ( p < 0.0001) inhibited 4-nitroaniline release, by 97.74% during the 10-min duration of the assay, which is indicative of tPA protease inhibition. In addition, two lead chromone cytoprotective candidates, 2-(3′,4′,5′-trihydroxyphenyl)chromen-4-one (3′,4′,5′-trihydroxyflavone) (CSMC-19) and 3-hydroxy-2-[3-hydroxy-4-(pyrrolidin-1-yl)phenyl]benzo[h]chromen-4-one (CSMC-140), also significantly ( p < 0.05) reduced 4-nitroaniline accumulation, but to a lesser extent. The reduction was 68 and 45%, respectively, at 10 μM, and extrapolated IC values were 4.37 and >10 μM for CSMC-19 and CSMC-140, respectively. Using bonafide 4-nitroaniline, we then demonstrated that the reduction of 4-nitroaniline detection was not due to drug-4-nitroaniline quenching of signal detection at OD. In conclusion, the results suggest that high concentrations of both cytoprotectives reduced 4-nitroaniline production in vitro, but the inhibition only occurs with concentrations 104-1025-fold that of EC values in an efficacy assay. Thus, CSMC-19 and CSMC-140 should be further developed and evaluated in embolic stroke models in the absence or presence of a thrombolytic. If necessary, they could be administered once effective tPA thrombolysis has been confirmed to avoid the possibility that the chromone will reduce the efficacy of tPA in patients. Stroke investigator developing new cytoprotective small molecules should consider adding this sensitive assay to their development and screening repertoire to assess possible drug-tPA interactions in vitro as a de-risking step. [ABSTRACT FROM AUTHOR]

Diabetes worsens stroke outcome and increases the risk of hemorrhagic transformation (HT) after ischemic stroke, especially with tissue plasminogen activator (tPA) treatment. The widespread use of tPA is still limited by the fear of hemorrhagic transformation (HT), and underlying mechanisms are actively being pursued in preclinical studies. However, experimental models use a 10 times higher dose of tPA than the clinical dose (10 mg/kg) and mostly employ only male animals. In this translational study, we hypothesized that low-dose tPA will improve the functional recovery after the embolic stroke in both control and diabetic male and female animals. Diabetes was induced in age-matched male and female Wistar rats with high fat diet and low-dose streptozotocin (30 mg/kg, i.p.). Embolic stroke was induced with clot occlusion of the middle cerebral artery (MCA). The animals were treated with or without tPA (1 mg/kg, i.v.) at 90 min after surgery. An additional set of animals were subjected to 90 min MCAO with suture. Neurological deficits (composite score and adhesive removal test-ART), infarct size, edema ratio, and HT index were assessed 3 days after surgery. In the control groups, female rats had smaller infarcts and better functional outcomes. tPA decreased infarct size in both sexes with a greater effect in males. While there was no difference in HT between males and females without tPA, HT was less in the female + tPA group. In the diabetic groups, neuronal injury increased in females reaching that of the infarct sizes seen in male rats. tPA decreased infarct size in females but not males. HT was greater in female rats than in males and was not further increased with tPA. Diabetes worsened neurological deficits in both sexes. Male animals showed improved sensorimotor skills, especially with tPA treatment, but there was no improvement in females. These data suggest that diabetes amplifies neurovascular injury and neurological deficits in both sexes. Human dose tPA offers some degree of protection in male but not female rats. Given that control female animals experience less injury compared to male rats, the diabetes effect is more profound in females. [ABSTRACT FROM AUTHOR]

Roughly one-third of all strokes are caused by an embolus traveling to a cerebral artery and blocking blood flow in the brain. The objective of this study is to gain a detailed understanding of the dynamics of embolic particles within arteries. Patient computed tomography image is used to construct a three-dimensional model of the carotid bifurcation. An idealized carotid bifurcation model of same vessel diameters was also constructed for comparison. Blood flow velocities and embolic particle trajectories are resolved using a coupled Euler-Lagrange approach. Blood is modeled as a Newtonian fluid, discretized using the finite volume method, with physiologically appropriate inflow and outflow boundary conditions. The embolus trajectory is modeled using Lagrangian particle equations accounting for embolus interaction with blood as well as vessel wall. Both one- and two-way fluid-particle coupling are considered, the latter being implemented using momentum sources augmented to the discretized flow equations. It was observed that for small-to-moderate particle sizes (relative to vessel diameters), the estimated particle distribution ratio-with and without the inclusion of two-way fluid-particle momentum exchange-were found to be similar. The maximum observed differences in distribution ratio with and without the coupling were found to be higher for the idealized bifurcation model. Additionally, the distribution was found to be reasonably matching the volumetric flow distribution for the idealized model, while a notable deviation from volumetric flow was observed in the anatomical model. It was also observed from an analysis of particle path lines that particle interaction with helical flow, characteristic of anatomical vasculature models, could play a prominent role in transport of embolic particle. The results indicate therefore that flow helicity could be an important hemodynamic indicator for analysis of embolus particle transport. Additionally, in the presence of helical flow, and vessel curvature, inclusion of two-way momentum exchange was found to have a secondary effect for transporting small to moderate embolus particles-and one-way coupling could be used as a reasonable approximation, thereby causing substantial savings in computational resources. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiac conditions. Atrial fibrillation (AF) has been demonstrated to be the most frequent arrhythmia encountered in HCM patients. Research focusing on AF and embolic stroke in HCM patients has been sparse and the sample size of most studies is small. The prognostic significance of AF in HCM patients is still not well known. The aim of this article is to provide further understanding of the anti-coagulation requirement of HCM patients with AF. [ABSTRACT FROM AUTHOR]

In vitro simulations of the trajectory and lodgement locations of emboli within the circle of Willis (CoW) are crucial in understanding the associated hemodynamic effects in stroke patients. A clot was fabricated from the hemolymph of a crustacean species. Clots were injected into the internal carotid artery via a cerebral flow facility housing a manufactured CoW human model. The trajectory of the clot was tracked and its hemodynamic effects monitored. The clots traveled with an average velocity of 88 mm/s along the ipsilateral side with momentary pauses along high curvature regions before finally lodging within the distal branches of the ipsilateral middle cerebral artery (MCA). These clots either elongated along the branching vessels or compressed against a bifurcation point. A blocked M1-segment of the MCA reduced the efferent blood pressure and flow rates by (15-77%) and (20-100%) respectively with a re-distribution of the flow towards the other efferent vessels. Mimicking blood clots with crustacean hemolymph provides a much lower biohazard risk than using human or mammalian blood clots and a superior alternative to synthetic materials. The geometry of the distal MCA vasculature will determine the end morphology of the lodged clot. Clotting severely reduces the distal flow rates and pressures. [ABSTRACT FROM AUTHOR]

Acute hyperglycemia (HG) exacerbates reperfusion injury and aggravates tissue plasminogen activator (tPA)-induced hemorrhagic transformation (HT). Previous experimental hyperglycemic stroke studies employed very high blood glucose levels and exclusively used suture occlusion model to induce ischemia. Only few studies evaluated HG in embolic stroke and mostly involving the use of 10-fold higher dose of tPA than that is used in patients. However, the interaction between acute HG and low (human) dose tPA in different experimental models of stroke has never been reported. We first tested the impact of the severity of acute HG on stroke outcome. Building upon our findings, we then compared the impact of mild acute HG on neurovascular injury in rats subjected to suture or thromboembolic occlusion with and without low dose tPA. We assessed cerebral blood flow, neurobehavioral outcomes, infarction, hemorrhage, and edema. tPA did not change the infarct size in either control or hyperglycemic animals when compared to no tPA groups. HG increased HT and worsened functional outcomes in both suture and embolic occlusion models. The combination of HG and tPA exacerbated the vascular injury and worsened the neurological deficits more than each individual treatment in both models. Our findings show that the interaction between HG and even low dose tPA has detrimental effects on the cerebrovasculature and functional outcomes independent of the method of reperfusion. [ABSTRACT FROM AUTHOR]

Redox imbalance in the brain significantly contributes to ischemic stroke pathogenesis, but antioxidant therapies have failed in clinical trials. Activation of endogenous defense mechanisms may provide better protection against stroke-induced oxidative injury. TXNIP (thioredoxin-interacting protein) is an endogenous inhibitor of thioredoxin (TRX), a key antioxidant system. We hypothesize that TXNIP inhibition attenuates redox imbalance and inflammation and provides protection against a clinically relevant model of embolic stroke. Male TXNIP-knockout (TKO), wild-type (WT), and WT mice treated with a pharmacological inhibitor of TXNIP, resveratrol (RES; 5 mg/kg body weight), were subjected to embolic middle cerebral artery occlusion (eMCAO). Behavior outcomes were monitored using neurological deficits score and grip strength meter at 24 h after eMCAO. Expression of oxidative, inflammatory, and apoptotic markers was analyzed by Western blot, immunohistochemistry, and slot blot at 24 h post-eMCAO. Our result showed that ischemic injury increases TXNIP in WT mice and that RES inhibits TXNIP expression and protects the brain against ischemic damage. TKO and RES-treated mice exhibited a 39.26 and 41.11 % decrease in infarct size and improved neurological score and grip strength compared to WT mice after eMCAO. Furthermore, the levels of TRX, nitrotyrosine, NOD-like receptor protein (NLRP3), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and activations of caspase-1, caspase-3, and poly-ADP-ribose polymerase (PARP) were significantly ( P < 0.05) attenuated in TKO and RES-treated mice. The present study suggests that TXNIP is contributing to acute ischemic stroke through redox imbalance and inflammasome activation and inhibition of TXNIP may provide a new target for therapeutic interventions. This study also affirms the importance of the antioxidant effect of RES on the TRX/TXNIP system. [ABSTRACT FROM AUTHOR]

Remote ischemic conditioning is neuroprotective in young male rodents after experimental stroke. However, it has never been tested in females whom remain at higher risk of stroke injury after menopause. We tested remote ischemic perconditioning therapy (RIPerC) at 2 h after embolic stroke in ovariectomized (OVX) female mice with and without intravenous tissue plasminogen activator (IV-tPA) treatment. We assessed cerebral blood flow (CBF), neurobehavioral outcomes, infarction, hemorrhage, edema, and survival. RIPerC therapy with and without IV-tPA improved the CBF and neurobehavioral outcomes and reduced the infarction, hemorrhage, and edema significantly. Late IV-tPA alone at 4 h post-stroke neither improved the neurobehavior nor reduced the infarction but aggravated hemorrhage and mortality in OVX mice. RIPerC therapy prevented the increased mortality during late IV-tPA. Our study demonstrates for the first time that RIPerC therapy is effective in OVX females. [ABSTRACT FROM AUTHOR]

We have previously reported that angiotensin receptor blockade reduces reperfusion hemorrhage in a suture occlusion model of stroke, despite increasing matrix metalloproteinase (MMP-9) activity. We hypothesized that candesartan will also decrease hemorrhage associated with delayed (6 h) tissue plasminogen activator (tPA) administration after embolic stroke, widening the therapeutic time window of tPA. Adult male Wistar rats were subjected to embolic middle cerebral artery occlusion (eMCAO) and treated with either candesartan (1 mg/kg) alone early at 3 h, delayed tPA (10 mg/kg) alone at 6 h, the combination of candesartan and tPA, or vehicle control. Rats were sacrificed at 24 and 48 h post-eMCAO and brains perfused for evaluation of neurological deficits, cerebral hemorrhage in terms of hemoglobin content, occurrence rate of hemorrhage, infarct size, tissue MMP activity and protein expression. The combination therapy of candesartan and tPA after eMCAO reduced the brain hemorrhage, and improved neurological outcome compared with rats treated with tPA alone. Further, candesartan in combination with tPA increased activity of MMP-9 but decreased MMP-3, nuclear factor kappa-B and tumor necrosis factor-α expression and enhanced activation of endothelial nitric oxide synthase. An activation of MMP-9 alone is insufficient to cause increased hemorrhage in embolic stroke. Combination therapy with acute candesartan plus tPA may be beneficial in ameliorating tPA-induced hemorrhage after embolic stroke. [ABSTRACT FROM AUTHOR]

Using the information of the federal statistics, a detailed description of the hospitalisation rate for cranial and non-cranial embolic events in Germany is given for the years 2005–2010. Detailed lists of the ICD codes I63.0 (stroke) and I74 (arterial embolism and thrombosis) as principal diagnosis and of I48.0 (atrial fibrillation) as additional diagnosis for the years 2005–2010 were provided by the Federal Statistical Office. In the 6 years period total number of cases hospitalised for stroke increased by 24 % (from 185.026 to 229.798) and those hospitalised for embolic events by 60 % (from 64,106 to 92,428). The number of atrial fibrillation as a major cause of arterial embolism documented as additional diagnosis increased by 38 % (from 1.06 to 1.48 Mio). Considering the rate per 100,000 inhabitants, intra-cranial embolism showed the most relevant increase with about 56 % since 2005. Cranial embolism is around 2.5 to 4 times more frequent than non-cranial embolism in females aged 70 to 80 years, but only two times in females aged 40–50, 50–60 and 90 years and older. Males showed a similar distribution with a broader peak. From 2005 to 2010 the total number of embolic events increased, with a higher increase in cranial embolism compared to non-cranial embolism. [ABSTRACT FROM AUTHOR]

Introduction: Hypertonic saline (HS) can treat cerebral edema arising from a number of pathologic conditions. However, physicians are reluctant to use it during the first 24 h after stroke because of experimental evidence that it increases infarct volume when administered early after reperfusion. Here, we determined the effect of HS on infarct size in an embolic clot model without planned reperfusion. Methods: A clot was injected into the internal carotid artery of male Wistar rats to reduce perfusion in the middle cerebral artery territory to less than 40 % of baseline, as monitored by laser-Doppler flowmetry. After 25 min, rats were randomized to receive 10 mL/kg of 7.5 % HS (50:50 chloride:acetate) or normal saline (NS) followed by a 0.5 mL/h infusion of the same solution for 22 h. Results: Infarct volume was similar between NS and HS groups (in mm: cortex 102 ± 65 mm vs. 93 ± 49 mm, p = 0.72; caudoputamenal complex 15 ± 9 mm vs. 21 ± 14, p = 0.22; total hemisphere 119 ± 76 mm vs. 114 ± 62, p = 0.88, respectively). Percent water content was unchanged in the infarcted hemisphere (NS 81.6 ± 1.5 %; HS 80.7 ± 1.3 %, p = 0.16), whereas the HS-treated contralateral hemisphere was significantly dehydrated (NS 79.4 ± 0.8 %; HS 77.5 ± 0.8 %, p < 0.01). Conclusions: HS reduced contralateral hemispheric water content but did not affect ipsilateral brain water content when compared to NS. Infarct volume was unaffected by HS administration at all evaluated locations. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to evaluate the contributions of embolic etiologies, patent foramen ovale (PFO) and atrial septal aneurysm (ASA) to the pathogenesis of ischemic stroke in patients with antiphospholipid syndrome (APS). We performed transesophageal echocardiography (TEE) examination for consecutive stroke patients who had been diagnosed with APS (APS group) to detect potential embolic sources. APS was diagnosed based on the modified Sapporo criteria. The control stroke group comprised age- and sex-matched cryptogenic stroke patients undergoing TEE. We assessed and compared the clinical characteristics and TEE findings between stroke patients with APS and control stroke groups. Among 582 patients, nine patients (nine women; mean age, 50 ± 18 years) were classified into the APS group. In 137 patients undergoing TEE, 41 age-matched female stroke patients were recruited to the control stroke group. Prevalences of PFO and ASA were significantly higher in the APS group than in the control stroke group (89 vs. 41 %, p = 0.027; 67 vs. 20 %, p = 0.015, respectively). Multiple logistic regression analysis showed that PFO (odds ratio (OR), 13.71; 95 % confidence interval (CI), 1.01-185.62; p = 0.049) and ASA (OR, 8.06; 95 % CI, 1.17-55.59; p = 0.034) were independently associated with the APS group. PFO and ASA were strongly associated with the APS group, and could thus represent potential embolic sources in ischemic stroke patients with APS. [ABSTRACT FROM AUTHOR]

Mechanical clot retrieval is increasingly used for flow-restoration and thrombectomy in acute embolic stroke. Emerging as a treatment option in addition to intravenous or intra-arterial thrombolysis, it is currently being further developed and investigated as a potential first-line and stand-alone treatment. The ability to rapidly restore flow and effectively retrieve clots from large intracranial arteries is reflected by angiographic data and preliminary clinical results. This article reviews the principles and technical aspects of this new technique, its emergence from the spectrum of intravenous and endovascular stroke treatment, and summarizes the first clinical results for acute ischemic anterior and posterior circulation stroke. Clot retrieval devices are a very promising option for treatment of acute ischemic stroke in the setting of large vessel occlusion. However, there currently exists a reported discrepancy between excellent recanalization rates and less satisfactory clinical outcomes. This problem urgently needs to be addressed in a prospective randomized fashion and improvements of treatment be recognized and implemented before clot retrieval can be considered an established form of acute stroke treatment. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to investigate a novel device that was developed to direct emboli away from the internal carotid artery to the external carotid artery to prevent embolic stroke while avoiding the necessity for anticoagulation with warfarin. Methods: A stent-like, self-expandable filter was developed consisting of fine cobalt alloy mesh. After promising preclinical animal testing, the device was implanted into the common carotid artery extending into the external carotid artery in three patients with atrial fibrillation, each of whom were at high-risk for cerebral emboli and were suboptimal candidates for anticoagulation. Follow-up was performed clinically and with carotid duplex ultrasound. Results: The implantation was successful in all three patients. Unrestricted flow through the filter was demonstrated in each patient at 6 months by duplex sonography. However, at 7 months ultrasound demonstrated occlusion of the internal carotid artery filter in one patient, which was subsequently confirmed by angiography. Subtotal filter occlusion occurred in a second patient at 14 months. Neither patient had clinical symptoms. Both internal carotid arteries were successfully recanalized using standard angioplasty techniques without complication. The third patient had completely normal carotid blood flow at 29 months follow-up. Conclusions: Implantation of a novel device intended to divert emboli away from the internal carotid artery was feasible, but resulted in occlusive neointimal proliferation in two of three patients. These results demonstrate a discrepancy from the findings of preclinical animal studies and human investigation. [ABSTRACT FROM AUTHOR]

Purpose: Assuming thromboembolic events to be the origin of silent strokes during cerebral digital subtraction angio-graphy (DSA), antiplatelet therapy with acetylsalicylic acid (ASA) should significantly reduce the risk for DSA-related silent stroke. The aim of this retrospective analysis was to assess whether ASA does prevent DSA-related silent stroke in terms of high signal intensity lesions in diffusion-weighted magnetic resonance imaging (DW-MRI). Methods: All patients underwent a baseline DW-MRI 24 h before DSA and a follow-up DW-MRI 3-24 h after DSA. Patients were considered to have an acute (silent) infarction caused by DSA if there was at least one hyperintense lesion of at least 1 mm in diameter and no neurological deficits. Results: Out of 52 patients in the ASA group 11 (21.2%) had high signal lesions on DW-MRI and 20 out of 123 (16.3%) in the non-ASA group. No significant relationship between the ASA and non-ASA group and the post-angiographic appearance of high signal intensity lesions in DW-MRI could be found (Wilcoxon 2-sample test: p-value 0.9). Conclusions: The use of oral antiplatelet therapy by ASA (100 mg/day) in cerebrovascular patients did not prevent DSA-related high signal intensity lesions in DW-MRI in this study. Despite a potential bias of this retrospective analysis the findings challenge the current theory of thromboembolisms being the predominant origin of silent stroke. The findings therefore support alternative hypotheseses of the etiology of silent strokes, such as air embolism and mobilized embolic material by the catheter at the vessel wall. [ABSTRACT FROM AUTHOR]

Identifying atrial fibrillation (AF) as the cause of stroke is important because it may trigger a change from therapy with antiplatelet agents to proven superior therapy with anticoagulants. Ischemic stroke due to chronic AF is readily diagnosed, but if patients with intermittent AF remain in sinus rhythm throughout their hospitalization, they will likely be discharged on inferior treatment. Numerous monitoring techniques can identify intermittent AF, and the available evidence suggests that prolonging the duration of monitoring increases the likelihood of detecting AF, which supports the use of monitoring beyond the currently recommended 24 h. Further research is required to definitively establish the utility of cardiac monitoring and identify the optimum method and duration. The promise of new drugs to replace warfarin in the near future reinforces the importance of this line of research. Even using current therapeutics, optimizing the diagnosis of AF remains a key component of quality care for patients with ischemic stroke. [ABSTRACT FROM AUTHOR]

To assess the use of antithrombotic therapy among atrial fibrillation (AF) patients in a Brazilian University Heart Hospital (InCor). In a cross-sectional study we analyzed the charts of all patients treated at InCor in five separate days of 2002 (Phase 1). To assess the impact of admission to a cardiology hospital, a follow-up of the AF patients selected in Phase 1 was carried out after 1 year (Phase 2). The prevalence of AF in the 3,764 assessed charts was 8.0% (301 patients). In Phase 1, antiplatelets were prescribed to 21.2% and anticoagulant therapy (ACT) to 46.5% of AF patients; in Phase 2, to 19.9 and 57.8%, respectively. Thus, 32.2% (Phase 1) and 22.2% (Phase 2) of AF patients were not receiving any antithrombotic drug. Among AF patients with previous ischemic stroke (17.6%), only 49% (Phase 1) and 60.4% (Phase 2) were receiving ACT. As many as 34 and 22.6%, respectively, were not receiving any antithrombotic drug. After follow-up, a new acute embolic event was documented in 5.6% of patients, 17% died. Anticoagulation is underused in AF patients and neither the fact of being treated by cardiologists in a University Hospital, nor the learning time-window of 1 year seemed to improve the antithrombotic care significantly. [ABSTRACT FROM AUTHOR]

The post-thrombotic brain has recently been reported to have an enhanced vulnerability to a second embolic insult. Although postischemic hypothermia is neuroprotective in global and focal ischemia models, the effect of mild hypothermia on outcome after thromboembolic insults has not been evaluated. This study therefore determined whether brain hypothermia (33°C) was neuroprotective against repeated thromboembolic insults. Photochemically induced non-occlusive common carotid artery thrombosis (CCAT) leading to platelet embolization to the brain was induced in anesthetized rats (n=35). Thirty minutes after CCAT, brain temperature was maintained at normothermic (37°C) or hypothermic (33°C) levels for 4 h followed by a slow rewarming period (1.5 h). Three days later, rats underwent a secondary CCAT insult under normothermic conditions and were allowed to survive for an additional 3 days prior to perfusion fixation and quantitative histopathological assessment. Compared to normothermic animals, mild hypothermia after the first embolic insult produced a significant reduction (P>0.05) in overall infarct volume. Hypothermia reduced total infarct volume from 7.55±2.32 mm3 (mean ± SEM) in normothermic rats to 2.56±0.88 mm3 in hypothermic animals undergoing repeated insults. Histopathological analysis also demonstrated less evidence for focal hemorrhage in the cooled groups. These data demonstrate that mild hypothermia is protective in a thromboembolic stroke model. In addition, post-thrombotic hypothermia decreases the histopathological vulnerability of the post-thrombotic brain to secondary embolic insults. These findings may be important in the prevention of stroke in patients at risk. [ABSTRACT FROM AUTHOR]

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Distribution and number of ischemic cerebrovascular events were studied in 57 patients who suffered from heart disorders with proven or highly probable source of cardiac embolism and compared to 39 patients with ulcerations of the craniocervical vessels. Patients with coexisting lesions were excluded from the present study. Out of the 57 patients with cardiac disorders, a single episode of cerebral embolism occurred in 33 patients. Of the 24 patients with recurrent ischemic episodes, different vascular territories were involved in only six cases. There was no evidence of a distinct distribution of vascular territories involved in cerebral embolism. The left middle cerebral artery was affected in 42.9%, the right middle cerebral artery in 23.8%, the vertebrobasilar territory in 19%, and the ophthalmic arteries in 14.2%. Statistical analysis revealed no significant differences in lesion localization between the group with a cardiac source of embolism and the group with ulcerations of the craniocervical vessels. There was a high frequency of patients with recurrent cardiogenic emboli in the ophthalmic (6 of 9 patients) as well as in the vertebrobasilar (6 of 12 patients) circulation who experienced a delayed initiation of cardiac assessment. The possibility of cardiac embolism should be considered in any patient with cerebral ischemia, independently of the vascular territory affected. [ABSTRACT FROM AUTHOR]

Two and a half million Americans with atrial fibrillation are at an elevated risk for embolic stroke. Warfarin therapy is standard treatment for high-risk patients, yet 40–65% of elderly patients do not receive anticoagulation therapy due to bleeding complications. To address this clinical need, we are evaluating a minimally invasive stent-based stroke prevention device to divert emboli from entering the arterial supply of the brain. The feasibility of a J-shaped stroke prevention device was tested in a mock circulatory loop. Sixteen sets of 100 simulated emboli (1–5 mm3) were injected into the left atrium with and without J stents protecting the aortic arch vessels. To determine efficacy, emboli were trapped in filters in the aortic arch vessels and distal aorta for manual counting. J stents decreased the number of emboli that entered the brachiocephalic trunk by 93.7% ( p < 0.0001), left common carotid artery by 79.8% ( p < 0.0001), and left subclavian artery by 89.7% ( p < 0.0001). In a mock circulation, J stents positioned in the aortic arch vessels and oriented downstream of aortic flow significantly decreased the number of emboli that entered the aortic arch vessels. These results warrant further investigation to determine the safety and efficacy of this prophylactic intervention to reduce embolic events, and chronic large animal studies are underway. [ABSTRACT FROM AUTHOR]

A case of left atrial appendage aneurysm is described in a 40-year-old man, who presented with recurrent embolic strokes and was asymptomatic until the last 6 months. Chest X-ray revealed a slightly prominent upper left heart border. The diagnosis was made by transthoracic two-dimensional echocardiography and confirmed by transesophageal echocardiography, magnetic resonance imaging and also by surgery. [ABSTRACT FROM AUTHOR]