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Background and Purpose: In order to assess the association of microparticles derived from activated platelets (PMP) or endothelial cells (EMP) with risk markers for recurrent embolic events in patients with symptomatic carotid artery disease, we studied the associations between PMP/EMP and three risk markers: plaque haemorrhage (PH), micro-embolic signals and cerebral diffusion abnormalities., Methods: Patients with recently symptomatic high-grade carotid artery stenosis (60-99%, 42 patients, 31 men; mean age 75 ± 8 years) and 30 healthy volunteers (HV, 11 men; mean age 56 ± 12 years) were prospectively recruited. Patients were characterised by carotid magnetic resonance imaging (presence of PH [MRI PH]), brain diffusion MRI (cerebral ischaemia [DWI+]) and transcranial Doppler ultrasound (micro-embolic signals [MES+]). PMP and EMP were classified by flow cytometry and expressed as log-transformed counts per microlitre., Results: MES+ patients (n = 18) had elevated PMP (MES+ 9.61 ± 0.57) compared to HV (8.80 ± 0.73; p < 0.0001) and to MES- patients (8.55 ± 0.85; p < 0.0001). Stroke patients had elevated PMP (9.49 ± 0.64) and EMP (6.13 ± 1.0) compared to non-stroke patients (PMP 8.81 ± 0.73, p = 0.026, EMP 5.52 ± 0.65, p = 0.011) and HV (PMP 8.80 ± 0.73, p = 0.007, and EMP 5.44 ± 0.47, p = 0.006). DWI+ patients (n = 16) showed elevated PMP (DWI+ 9.53 ± 0.64; vs. HV, p = 0.002) and EMP (DWI+ 5.91 ± 0.99 vs. HV 5.44 ± 0.47; p = 0.037). Only PMP but not EMP were higher in DWI+ versus DWI- patients (8.67 ± 0.90; p = 0.002). No association was found between PMP and EMP with MRI PH., Conclusions: PMP and EMP were associated with stroke and recent cerebrovascular events (DWI+) but only PMP were also associated with ongoing (MES+) thrombo-embolic activity suggesting a differential biomarker potential for EMP to index cerebral ischaemia while PMP may predict on-going thrombo-embolic activity., (The Author(s). Published by S. Karger AG, Basel.)

Object: We investigated possible associations among the presence of cholesterol crystals in embolic debris, the proportions of debris components, and postoperative cerebral embolism in patients undergoing carotid artery stenting (CAS)., Methods: Sixty-seven consecutive procedures were performed for internal carotid artery stenosis with CAS at our hospital between November 2015 and February 2018. Procedures for emergency CAS for stroke in evolution or crescendo transient ischemic attack were excluded (n = 12). The embolic debris from remaining procedures (n = 55) was stained with hematoxylin-eosin and the red blood cells, white blood cells, and fibrin were quantified by color-based segmentation. Cholesterol crystals and calcification were examined histopathologically. Diffusion-weighted imaging (DWI) was performed 1-3 days after CAS, and the images were used to classify procedures according to the presence of new lesions., Results: Of the 55 CAS procedures, new DWI lesions were identified after 32. One patient had symptomatic cerebral embolism. Higher proportions of patients with cholesterol crystals in embolic debris (17 vs. 78%, p < 0.001) and higher proportion of white blood cells (mean 2.3 [0-9.9] vs. 4.2% [0-29.9%], p < 0.01) were observed in the embolic debris of procedures with and without new DWI lesions., Conclusions: Cholesterol crystals were common in the embolic debris from patients with postoperative ischemic lesions after CAS. These results suggest that inflammatory destabilization of the intraplaque lipid component is related to postprocedural DWI lesions., (© 2019 S. Karger AG, Basel.)

Background: Embolic infarctions from the heart are known to cause multiple scattered infarct lesions as well as single, large territorial infarctions. However, it remains unknown which factors contribute to these different infarction patterns in patients with potential cardiac sources of embolism (PCSE)., Methods: We examined 388 ischemic stroke patients with a high-risk PCSE using diffusion-weighted imaging. Infarction patterns were categorized into a single large lesion, a single small lesion, confluent and additional lesions, or small scattered lesions. The relationships between infarction patterns and clinical and hematologic parameters were investigated., Results: Of the 388 patients, a single large lesion was detected in 139 (35.8%), a single small lesion in 29 (7.5%), confluent and additional lesions in 171 (44.1%), and small scattered lesions in 49 (12.7%). Prior use of antiplatelet agents and anticoagulant were associated with the pattern of small scattered lesions and a single small lesion, respectively. Additionally, higher white blood cell counts were associated with confluent and additional lesions. The type of high-risk PCSE was not related to a specific infarction pattern., Conclusions: These results suggest that platelet function and inflammatory processes may directly affect the thrombus formation in the cardiac chamber., (Copyright © 2011 S. Karger AG, Basel.)

Background and Purpose: The purpose of the present study was to clarify the difference in the infarct topography on diffusion-weighted image (DWI) and cardiac and aortic findings on transesophageal echocardiography (TEE) in stroke patients with different embolic sources., Methods: We studied 270 consecutive patients with acute ischemic stroke who had DWI-documented cortical or subcortical infarcts without significant stenosis of the cerebral arteries. As embolic sources, cardiac diseases, right-to-left shunt diseases and an aortic arch atheroma ≥4.0 mm in thickness were identified using various diagnostic tools including TEE., Results: Seventy-eight (29%) patients had multiple embolic sources. Large infarcts were common in patients in whom cardiac disease was the only embolic source and uncommon in patients in whom aortic atheroma was the only embolic source (p < 0.0001). Vertebrobasilar infarcts were relatively common in patients only having aortic atheromas. Atrial septal aneurysms were more common in patients with a right-to-left shunt than in those with a shunt plus other embolic sources (p = 0.0036). Unique characteristics of the arch atheroma (mobile plaque, extension to branches, or ulcer formation; p < 0.0001) as well as small or moderate-sized infarcts (p = 0.0004) were more common in patients with arch atheromas as the only embolic source than in those with atheromas plus other embolic sources., Conclusions: Embolic stroke patients often have multiple embolic sources. The present study suggests the possibility that embolic stroke has unique clinical features depending on its source. DWI and TEE findings might be helpful in characterizing cardiogenic, paradoxical and aortogenic brain embolism., (Copyright © 2011 S. Karger AG, Basel.)

Background: The natural history of cerebral arteriovenous malformations (AVMs) is yet to be determined. It has been shown that angiogenic factors are involved in the pathogenesis of AVMs, in particular in partially embolized lesions. This study was conducted to investigate the expression of angiogenic and proliferative factors in relation to different clinical conditions and treatment modalities., Methods: Immunohistochemistry was performed for 145 consecutive cases of cerebral AVMs. The specimens were stained with antibodies against VEGF, bFGF, Ki 67, CD 34 and CD 31. Expression was correlated with clinical presentation (haemorrhage, seizures or other symptoms), AVM localization, size, eloquence and venous drainage, as well as with preoperative AVM embolization., Results: Whereas no correlation was found between the expression of angiogenic factors and different clinical conditions, we observed a significantly increased proliferation activity as shown by Ki 67 expression in patients with intracerebral haemorrhage (p = 0.02) and in patients with preoperative embolization (p = 0.02)., Conclusions: Increased proliferation activity in partially embolized AVMs supports a 'no-touch' strategy and clinical observation in high-risk AVMs and demands complete AVM elimination in treatable lesions., (Copyright (c) 2010 S. Karger AG, Basel.)

Background and Purpose: It is still controversial whether the nature of cerebral infarcts differs between cancer patients and the general population. The aim of this study is to delineate the characteristics of acute cerebral infarction in patients with active malignancy using diffusion-weighted imaging (DWI)., Materials and Methods: Seventy consecutive patients with both active malignancy and acute cerebral infarction (confirmed by DWI) were retrospectively included. These 70 were divided into 3 groups on the basis of infarct pattern: embolic infarction, large artery disease, and lacunar infarction. Medical records were reviewed in detail for demographic data, cancer information, vascular risk factors, and prognosis., Results: Two thirds of cancer patients had multiple infarcts, and 30% of infarcts were located infratentorially. Embolic infarction, large artery disease, and lacunar infarction occurred in 60, 31, and 9% of cancer patients, respectively. Gastrointestinal (GI) cancer was significantly related to embolic infarction (odds ratio 4.64, p = 0.04). The 3-month mortality rates were higher in patients with rather than without cancer metastasis (68 vs. 8%; p < 0.001)., Conclusions: Cerebral infarcts in cancer patients tended to be embolic and multiple. Patients with GI cancer were particularly susceptible to embolic infarction., (Copyright 2009 S. Karger AG, Basel.)

Background and Purpose: We have noted the presence of small strip-like infarcts involving the cortex within the interdivisional territory of the middle cerebral artery (MCA) and sometimes extending to the periventricular region. The incidence in a stroke unit population, mechanisms, clinical expression and prognosis of patients with these cortical infarcts are unknown. To clarify these issues we retrospectively and prospectively identified these patients in our own stroke unit population., Methods: Patients were identified retrospectively and prospectively from the Austin Hospital Stroke Unit from March 2001 to May 2007. All were selected on the basis of the recent onset of an acute neurological deficit with imaging showing strip infarction within the MCA territory. Clinical features were recorded and the mechanism of infarction was classified based on the TOAST criteria from standard investigations., Results: From 4,274 acute stroke admissions, there were 24 patients (0.6%), 12 males and 12 females (mean age 75 years; range 44-92 years) with CT or MRI showing characteristic linear infarction in the middle cerebral territory. In most cases, infarction was adjacent to the central sulcus. Common clinical features included mild-to-moderate hemiparesis with cortical signs. The most common TOAST criterion mechanism categories were artery-to-artery or cardiac embolism. It is postulated that this resulted in either isolated small cortical artery branch occlusion or borderzone infarction between superior and inferior divisions of the MCA due to more proximal large-artery vessel occlusion. Prognosis was good., Conclusions: We describe the phenotypic expression, postulated mechanisms and prognosis of strip-like infarcts between the superior and inferior MCA divisions. The likely artery-artery or cardio-embolic mechanisms should prompt clinicians to search for an embolic source. While the prognosis of the syndrome is generally good, its recognition may allow specific therapies to be developed to improve clinical outcomes further.

A new subtype classification of ischemic stroke was developed to reflect recent therapeutic strategies as well as evolving concepts of stroke definitions and mechanisms. In 200 consecutive patients with acute ischemic stroke, the inter-rater reliability and proportion of subtypes of the new classification system were assessed and compared with those of the Trial of ORG 10172 in the Acute Stroke Treatment (TOAST) classification. The most frequent subtype of the new classification was atherothrombosis (n = 80, 40%), followed by stroke of undetermined etiology (n = 54, 27%), small artery disease (n = 33, 16.5%), cardioembolism (n = 26, 13%), and stroke of other determined etiology (n = 7, 3.5%). Three raters agreed to the stroke subtype diagnosis in 165 out of 200 cases and the overall kappa value was excellent (kappa = 0.82). The new classification system for brain infarction was easy to use and had high inter-rater reliability., (Copyright 2007 S. Karger AG, Basel.)

Background: The clinical relevance of the microembolic signals (MES) detected by transcranial Doppler sonography (TCD) in acute stroke remains unclear. In a prospective study the authors analyzed the relationship between MES and the findings on diffusion-weighted magnetic resonance imaging (DWI) in acute stroke patients., Methods: We performed TCD for a period of 30 min to detect MES in patients within 24 h of stroke onset, and DWI was done within the initial 7 days. MES were assessed from Doppler waves obtained from the middle cerebral artery contralateral to the side of the neurological deficits. The acute ischemic lesions observed on DWI were classified by their diameter (small, medium or large) and by their site (cortical, superficial perforator territory, internal borderzone or deep perforator territory)., Results: We obtained Doppler waves from 39 vessels in 37 patients; 2 patients had bilateral deficits. MES were detected in 12 vessels (MES-positive group) and not detected in 27 vessels (MES-negative group). No significant differences in clinical features were observed between the 2 groups. The number of small lesions was significantly higher in the MES-positive group than in the MES-negative group (p = 0.02). The numbers of cortical and superficial perforator infarcts were significantly higher in the MES-positive group than in the MES-negative group (p = 0.002 and 0.02, respectively)., Conclusion: In acute ischemic stroke, MES detected by TCD in the acute phase may produce small cortical and subcortical lesions found on DWI., ((c) 2007 S. Karger AG, Basel.)

Background and Purpose: The clinical, etiological and stroke mechanisms are defined well before but the detailed clinical and etiologic mechanisms regarding to all clinical spectrum of posterior inferior cerebellar artery (PICA) infarcts were not systematically studied by diffusion-weighted imaging (DWI)., Methods: Seventy-four patients with PICA territory ischemic lesion proved by DWI with decreased apparent diffusion coefficient and FLAIR (fluid attenuation inversion recovery) included in our Registry, corresponding to 2% of 3,650 patients with ischemic stroke, were studied. The presence of steno-occlusive lesions in the posterior circulation were sought by magnetic resonance angiography, and reviewed with a three-dimensional rotating cineangiographic method., Results: We found six subgroups of PICA territory infarcts according clinico-topographical relationship: (1) 9 patients with lesion in the territory lateral branch of PICA; (2) 23 patients with an infarct in the territory of medial branch of PICA; (3) 9 patients with a lesion involving both medial and lateral branches of the PICA; (4) 9 patients with cortical infarcts at the boundary zones either between medial and lateral branches of the PICA or between PICA and m/l superior cerebellar artery (SCA); (5) 10 patients with a lesion at the deep boundary zones either between medial and lateral PICA, or between PICA and medial/lateral SCA; (6)14 patients with concomitant multiple lesions in the PICA and in other vertebrobasilar artery territories. The main cause of PICA infarcts was extracranial large-artery disease in 30 patients (41%) patients, cardioembolism and in situ branch disease in 15 patients (20%) each., Conclusions: Multiple PICA territory lesions on DWI were not uncommon and could be caused by multiple emboli originating from break-up of atherosclerotic plaque in the subclavian/innominate-vertebral arterial system. DWI findings of single or multiple small lesions could account for some cases with transient and subtle cerebellar symptoms which have been considered before as 'vertebrobasilar insufficiency' without morphologic lesion. Different clinical-DWI correlations allow us to determine better definition of the topographical and etiological spectrum of acute PICA territory lesions, which was previously defined by pathological and conventional MRI studies., (Copyright 2005 S. Karger AG, Basel.)

Ischaemic strokes and transient ischaemic attacks are commonly caused by cerebral embolism originating from formation of a platelet-rich thrombus superimposed on an atherosclerotic plaque or by atherothrombotic plaque rupture in a carotid or intracranial artery. Despite advances made through ultrasound imaging in our understanding of atherosclerotic plaque progression and regression, the issue of whether differences in plaque structure alone can distinguish between lesions that become symptomatic and others that remain clinically silent continues to be debated. Recent biochemical and imaging studies have identified characteristics that may reflect a high risk of vulnerability, such as outward, abluminal plaque remodelling, the presence of intra-plaque haemorrhage, inflammation, severe flow disturbances around the encroaching lesion, plaque cap thinning and ulceration, and abnormal plaque motion. Plaque stability may be improved through management of traditional cardiovascular risk factors or with biological or pharmacological agents that target pathways involved in plaque pathophysiology. Unstable plaques place patients at risk of unpredictable ischaemic events and in patients with such lesions, specific preventive treatment beyond long-term antiplatelet therapy can be used to prevent new or recurrent events., (Copyright 2004 S. Karger AG, Basel)

Background: Recent studies have suggested that previous infection may be a risk factor for ischemic stroke mainly in young and middle-aged patients. The present study sought to further investigate the association between recent inflammatory events (IE) and ischemic stroke without age restriction and to determine the role of recent IE in different ischemic stroke subtypes., Methods: We performed a case-control study with 93 consecutive hospitalized stroke patients and 200 (107 hospital and 93 community) controls. Acute IE, both infective and non-infective, occurring in the previous 30 days were assessed using a standard questionnaire. The TOAST criteria were used for ischemic stroke subtypes classification., Results: Acute IE in the previous 30 and 7 days were significantly and independently associated with ischemic stroke (37/93 vs. 47/200; OR 2.23, 95% CI 1.26-3.96 and 17/93 vs.16/200; OR 2.45, 95% IC 1.11-5.39, respectively). Stratifying for stroke subtypes, acute IE significantly and independently increased the risk of atherothrombotic (OR 5.72, 95% CI 2.14-15.25) and cardioembolic stroke (OR 3.02, 95%CI 1.20-7.63)., Conclusions: Acute IE increase the risk of acute ischemic stroke of atherothrombotic and cardioembolic type independently of other predisposing factors. Implications for daily clinical practice, in relation to prevention and treatment of IE in patients at risk, have to be explored., (Copyright 2003 S. Karger AG, Basel)