Search

Bicuspid aortic valve (BAV) is a common condition but is only rarely associated with embolic complications. We describe a 42-year-old man with recurrent posterior circulatory ischemic strokes that resulted in ataxia and cognitive impairment. Transesophageal echocardiography demonstrated a BAV with mild stenosis, moderate calcification, and a dilated ascending aorta. The degree of calcification and the valve phenotype might be important factors implicating the BAV as a rare cause of ischemic stroke., (Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Niaspan, an extended-release formulation of niacin (vitamin B3), has been widely used to increase high density lipoprotein (HDL) cholesterol and to prevent cardiovascular diseases and stroke. We have previously demonstrated that Niaspan (40 mg/kg) administered at 2h after stroke induces neuroprotection, while low dose Niaspan (20mg/kg) does not reduce infarct volume. Tissue plasminogen activator (tPA) is an effective therapy for acute stroke, but its use remains limited by a narrow therapeutic window. We have previously demonstrated that intravenous administration of tPA 4h after stroke in rats does not reduce infarct volume. In this study, we tested whether combination treatment with low-dose Niaspan (20mg/kg) and tPA administered 4h after embolic stroke in a rat model reduces infarct volume and provides neuroprotection., Methods: Adult male Wistar rats were subjected to embolic middle cerebral artery occlusion (MCAo) and treated with low-dose Niaspan (20mg/kg) alone (n = 7), tPA (10mg/kg) alone (n = 7), combination of low-dose Niaspan and tPA (n = 7), or saline control (n = 9), 4h after stroke. A battery of functional outcome tests was performed. Rats were sacrificed at 7 days after MCAo and lesion volumes were measured. To investigate the underlying mechanism of combination treatment neuroprotective effect, deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), cleaved caspase-3, tumor necrosis factor alpha (TNF-alpha), and toll-like receptor 4 (TLR-4) immunostaining were performed., Results: Combination treatment with low-dose Niaspan and tPA significantly improved functional outcome compared to the saline control group (p<0.05), while treatment with Niaspan or tPA alone did not significantly improve functional outcome compared to saline control group. Additionally, combination treatment significantly reduced infarct volume compared to saline control group (p = 0.006) and infarct volume was significantly correlated with functional outcome (p = 0.0008; r = 0.63). Monotherapy with Niaspan or tPA did not significantly decrease infarct volume compared to saline control group. Combination treatment reduced apoptosis as measured by significant reduction in the number of TUNEL-positive cells and cleaved caspase-3 expression in the ischemic brain compared to saline control group (p<0.05). Combination treatment also significantly reduced the expression of TNF-alpha and TLR-4 in the ischemic brain compared to Niaspan, tPA and saline treatment groups (p<0.05). A significant interaction between Niaspan and tPA on the TNF-alpha expression was detected (p<0.05), indicating a synergy effect in the combination treatment group., Conclusion: Treatment of stroke with combination of low-dose Niaspan and tPA at 4h after embolic stroke reduces infarct volume, improves neurological outcome and provides neuroprotection. The neuroprotective effects of combination treatment were associated with reduction of apoptosis and attenuation of TNF-alpha and TLR-4 expression., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objectives: The goal of this study was to compare the rate of cerebral microembolization during carotid artery stenting (CAS) with proximal versus distal cerebral protection in patients with high-risk, lipid-rich plaque., Background: Cerebral protection with filters partially reduces the cerebral embolization rate during CAS. Proximal protection has been introduced to further decrease embolization risk., Methods: Fifty-three consecutive patients with carotid artery stenosis and lipid-rich plaque were randomized to undergo CAS with proximal protection (MO.MA system, n = 26) or distal protection with a filter (FilterWire EZ, n = 27). Microembolic signals (MES) were assessed by using transcranial Doppler during: 1) lesion wiring; 2) pre-dilation; 3) stent crossing; 4) stent deployment; 5) stent dilation; and 6) device retrieval/deflation. Diffusion-weighted magnetic resonance imaging was conducted before CAS, after 48 h, and after 30 days., Results: Patients in the MO.MA group had higher percentage diameter stenosis (89 ± 6% vs. 86 ± 5%, p = 0.027) and rate of ulcerated plaque (35% vs. 7.4%; p = 0.019). Compared with use of the FilterWire EZ, MO.MA significantly reduced mean MES counts (p < 0.0001) during lesion crossing (mean 18 [interquartile range (IQR): 11 to 30] vs. 2 [IQR: 0 to 4]), stent crossing (23 [IQR: 11 to 34] vs. 0 [IQR: 0 to 1]), stent deployment (30 [IQR: 9 to 35] vs. 0 [IQR: 0 to 1]), stent dilation (16 [IQR: 8 to 30] vs. 0 [IQR: 0 to 1]), and total MES (93 [IQR: 59 to 136] vs. 16 [IQR: 7 to 36]). The number of patients with MES was higher with the FilterWire EZ versus MO.MA in phases 3 to 5 (100% vs. 27%; p < 0.0001). By multivariate analysis, the type of brain protection was the only independent predictor of total MES number. No significant difference was found in the number of patients with new post-CAS embolic lesion in the MO.MA group (2 of 14, 14%) as compared with the FilterWire EZ group (9 of 21, 42.8%)., Conclusions: In patients with high-risk, lipid-rich plaque undergoing CAS, MO.MA led to significantly lower microembolization as assessed by using MES counts., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: To review the outcome after endoscopic third ventriculostomy (ETV) for symptomatic, persistent hydrocephalus in three patients with perimesencephalic angiographically negative subarachnoid hemorrhage (PNH) who were dependent on an external ventricular drain (EVD)., Methods: All patients initially presented with severe headache, nuchal rigidity, confusion and lethargy (Hunt-Hess Grade II or III), and persistent, EVD-dependent hydrocephalus. Cranial CT images in each revealed acute hydrocephalus and perimesencephalic hemorrhage pattern with a heavy clot burden (Fisher grade 3). A 3D-CT angiogram on admission and two four-vessel cerebral angiograms failed to demonstrate a bleeding source. All three patients failed trial EVD clamping, with clinical deterioration and elevated intracranial pressure (ICP). ETV was performed with a 0-degree endoscope in a 4.6-mm irrigating sheath using an endoscopic-coring/"cookie-cut" technique. An EVD was left in place for postoperative ICP monitoring but was clamped., Results: ETV was accomplished in all patients. In one case, a tiny basilar tip aneurysm was seen during the endoscopic procedure. Intraoperatively, the prepontine cistern revealed dense, degraded blood products. Postprocedure ICP measurements were reduced to normal range. Clinical improvement, normal ICP readings, and/or radiographic evidence of resolution of hydrocephalus allowed uneventful removal of the EVD within 36-48 h post-ETV in all patients. All remained headache-free, with a normal neurological examination, during a follow-up period of 10, 11, and 12 months, respectively., Conclusion: To our knowledge, this is the first report of ETV for PNH with hydrocephalus and the first report of a basilar tip microaneurysm seen intraoperatively during ETV. ETV is a viable treatment option for refractory hydrocephalus secondary to a perimesencephalic pattern of subarachnoid hemorrhage (SAH). Its early application can avoid placement of a ventriculoperitoneal shunt, curtail the extended use of an EVD, and reduce the associated infection risks. Despite thorough angiographic investigation for an aneurysmal cause of SAH, a "microaneurysm" of the basilar artery was found at ETV. No complication or rebleeding was encountered.

Objective: Determining which small deep infarcts (SDIs) are of lacunar, arterial, or cardioembolic etiology is challenging, but important in delivering optimal stroke prevention therapy. We sought to distinguish lacunar from nonlacunar causes of SDIs using a gene expression profile., Methods: A total of 184 ischemic strokes were analyzed. Lacunar stroke was defined as a lacunar syndrome with infarction <15mm in a region supplied by penetrating arteries. RNA from blood was processed on whole genome microarrays. Genes differentially expressed between lacunar (n = 30) and nonlacunar strokes (n = 86) were identified (false discovery rate ≤ 0.05, fold change >|1.5|) and used to develop a prediction model. The model was evaluated by cross-validation and in a second test cohort (n = 36). The etiology of SDIs of unclear cause (SDIs ≥ 15mm or SDIs with potential embolic source) (n = 32) was predicted using the derived model., Results: A 41-gene profile discriminated lacunar from nonlacunar stroke with >90% sensitivity and specificity. Of the 32 SDIs of unclear cause, 15 were predicted to be lacunar, and 17 were predicted to be nonlacunar. The identified profile represents differences in immune response between lacunar and nonlacunar stroke., Interpretation: Profiles of differentially expressed genes can distinguish lacunar from nonlacunar stroke. SDIs of unclear cause were frequently predicted to be of nonlacunar etiology, suggesting that comprehensive workup of SDIs is important to identify potential cardioembolic and arterial causes. Further study is required to evaluate the gene profile in an independent cohort and determine the clinical and treatment implications of SDIs of predicted nonlacunar etiology., (Copyright © 2011 American Neurological Association.)

Objectives: We compared the safety of different devices by screening for subclinical intracranial embolic events after pulmonary vein isolation with either conventional irrigated radiofrequency (RF) or cryoballoon or multielectrode phased RF pulmonary vein ablation catheter (PVAC)., Background: New devices specifically designed to facilitate pulmonary vein isolation procedures have recently been introduced., Methods: This prospective, observational, multicenter study included patients with symptomatic atrial fibrillation referred for pulmonary vein isolation. Ablation was performed using 1 of the 3 catheters. Strict periprocedural anticoagulation, with intravenous heparin during ablation to achieve an activated clotting time >300 s, was ensured in all patients. Cerebral magnetic resonance imaging was performed before and after ablation., Results: Seventy-four patients were included in the study: 27 in the irrigated RF group, 23 in the cryoballoon group, and 24 in the PVAC group. Total procedure times were 198 ± 50 min, 174 ± 35 min, and 124 ± 32 min, respectively (p < 0.001 for PVAC vs. irrigated RF and cryoballoon). Findings on neurological examination were normal in all patients before and after ablation. Post-procedure magnetic resonance imaging detected a single new embolic lesion in 2 of 27 patients in the irrigated RF group (7.4%) and in 1 of 23 in the cryoballoon group (4.3%). However, in the PVAC group 9 of 24 patients (37.5%) demonstrated 2.7 ± 1.3 new lesions each (p = 0.003 for the presence of new embolic events among the 3 groups)., Conclusions: The PVAC is associated with a significantly higher incidence of subclinical intracranial embolic events. Further study of the causes and significance of these emboli is required to determine the safety of the PVAC., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Higher mean arterial pressure during cardiopulmonary bypass may improve cerebral outcome associated with cerebral air embolism by increasing emboli clearance and collateral flow to salvage the ischemic penumbra. However, this may come at the expense of increased delivery of embolic load. This study was designed to investigate the influence of mean arterial pressures on cerebral functional and histologic outcome after cerebral air embolism during cardiopulmonary bypass in an established rat model., Methods: Male Sprague-Dawley rats were exposed to 90 minutes of normothermic cardiopulmonary bypass with 10 cerebral air embolisms (0.3 μL/bolus) injected repetitively. Rats were randomized to 3 groups (n = 10, each) that differed in mean arterial pressure management during cardiopulmonary bypass: 50 mm Hg (low mean arterial pressure), 60 to 70 mm Hg (standard mean arterial pressure), and 80 mm Hg (high mean arterial pressure). Neurologic score was assessed on postoperative days 3 and 7 when cerebral infarct volumes were determined. Cognitive function was determined with the Morris water maze test beginning on postoperative day 3 and continuing to postoperative day 7., Results: Neurologic score was better in high and standard mean arterial pressure groups versus low mean arterial pressure groups. High mean arterial pressure resulted in shorter water maze latencies compared with standard and low mean arterial pressure on postoperative days 6 and 7. Total infarct volume and number of infarct areas were not different among groups., Conclusions: The use of higher mean arterial pressure during cardiopulmonary bypass in a rat model of cerebral air embolism conveyed beneficial effects on functional cerebral outcome with no apparent disadvantage of increased delivery of embolic load. Maintaining higher perfusion pressures in situations of increased cerebral embolic load may be considered as a collateral therapeutic strategy., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: To determine the incidence, time course, and severity of pulmonary fat embolism (PFE) and cerebral fat embolism (CFE) in trauma and nontrauma patients at the time of autopsy., Methods: Prospectively, consecutive patients presenting for autopsy were evaluated for evidence pulmonary and brain fat embolism. The lung sections were obtained from the upper and lower lobe of the patients' lungs on the right and left and brain tissue. This tissue was prepared with osmium tetroxide for histologic evaluation. The number of fat droplets per high power field was counted for all sections. The autopsy reports and medical records were used to determine cause of death, time to death, injuries, if cardiopulmonary resuscitation (CPR) was attempted, sex, height, weight, and age., Results: Fifty decedents were evaluated for PFE and CFE. The average age was 45.8 years ± 17.4 years, average body mass index was 30.1 kg/cm² ± 7.0 kg/cm², and 68% of the patients were men. The cause of death was determined to be trauma in 68% (34/50) of decedents, with 88% (30/34) blunt and 12% (4/34) penetrating. CPR was performed on 30% (15/50), and PFE was present in 76% (38/50) of all patients. Subjects with PFE had no difference with respect to sex, trauma, mechanism of injury, CPR, external contusions, fractures, head, spine, chest, abdominal, pelvic, and extremity injuries. However, subjects without PFE had significantly increased weight (109 ± 29 kg vs. 86 ± 18 kg; p = 0.023) but no difference in height or body mass index. PFE was present in 82% (28/34) of trauma patents and 63% (10/16) nontrauma patients. Eighty-eight percent of nontrauma patients and 86% of trauma patients who received CPR had PFE. Trauma patients with PFE showed no significant difference in any group. Eighty-eight percent of trauma patients died within 1 hour of injury, and 80% (24/30) of them had PFE at the time of autopsy. CFE was present only in one patient with a severe head and cervical spine injury., Conclusion: PFE is common in trauma patients. CPR is associated with a high incidence of PFE regardless of cause of death. PFE occurs acutely within the "golden hour" and should be considered in traumatically injured patients. Further studies are needed to evaluate the pathogenesis of PFE.

Objective: Cerebral embolization during trans-catheter aortic valve implantation (TAVI) has not been assessed clearly in the literature. Therefore, we compared the rate of cerebral embolisms with diffusion-weighted magnetic resonance imaging (DWI) in transfemoral (TF) and trans-apical (TA) approaches., Method: Eighty patients benefited from TAVI between January 2008 and June 2010. Out of these, 35 were included in the study. Twenty-one were TF (group 1) and 14 TA (group 2). During the same period, 285 patients benefited from a conventional aortic valve surgery (aortic valve replacement (AVR)). Thirteen of these were also analyzed and considered as the control group (group 3). We systematically performed a DWI the day before the procedure and 48 h after. DWI studies were blindly analyzed by a neuroradiologist, and all patients had a clinical neurological assessment before and after the procedure, according the National Institutes of Health Stroke Scale (NIHSS)., Results: Thirty-two patients in the TAVI group had new cerebral lesions: 19 in the TF group and 13 in the trans-apical group (p=NS). Mean number of embolic lesions per patient was 6.6 in group I and 6.0 in group II (p=NS). Mean volume of embolic lesions was 475.0 mm³ in group I and 2170.5 mm³ in group II (p=NS). In group III, one patient had one new cerebral lesion (p<0.05 vs TAVI) of 36.5 mm³ (p=NS vs TAVI). All patients were neurologically asymptomatic., Conclusions: The incidence of silent cerebral embolic lesions after TAVI is significantly higher compared with the standard surgical AVR. The number of emboli is similar in the TF and TA groups but the volume tended to be higher in the TA group. However, there is no clinical impact of those lesions., (Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Based on thrombus location and nature and anatomic features of aorta and cerebral arteries, we hypothesized that cardiogenic embolisms (CE) and aortogenic embolisms (AE) might have different right-left propensity and lesion patterns., Methods: We retrospectively reviewed patients with acute ischemic stroke with high-risk CE sources or moderate-or-severe aortic atherosclerotic plaques on transesophageal echocardiography. Lesion side and patterns on diffusion-weighted imaging were compared between CE and AE., Results: CE was identified in 123 and AE in 63. In multivariate analysis, right-sided lesions and corticosubcortical infarcts were independently associated with CE, and left-sided lesions and pial infarcts were independently associated with AE., Conclusions: CE and AE have different radiological characteristics, as shown by the right-left propensity and lesions patterns of cerebral infarcts.

It has long been debated whether watershed infarcts are caused by hemodynamic or embolic mechanisms. In the present study, we investigated microembolic roles in the pathogenesis of watershed infarcts by examining MRI in a macaque monkey model of multiple microinfarcts. 50 μm microbeads were injected into each internal carotid artery twice with a month interval. Monkeys (n=4) injected with 2250-2800 microbeads per unilateral side showed both cortical and internal watershed infarcts in the acute phase and atrophic changes with microbleeds in the chronic phase. These results suggest embolic pathogenesis can contribute to the genesis of both cortical and internal watershed infarcts in primates., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Following endoplasmic reticulum (ER) stress, cerebral infarctions have been reported to involve an apoptotic process, including the activation of the caspase cascade. To confirm whether fragmented caspase-12, which is activated by cleavage and is detectable during ER stress, is also involved in embolic cerebral infarctions in rats, we adopted an autologous blood clot model for the analysis of cerebral infarctions. We performed experiments in rats with brain infarctions, which are closely related to embolic cerebral infarctions. We utilized a homologous blood clot, i.e., natural materials, to form the infarct area. Our findings reveal that caspase-12 is fragmented when infarct areas form in cerebral cortical neurons. Interestingly, we observed that these fragments translocated to the nuclei of not only cerebral cortical neurons but hippocampal neurons. We further found that glucose-regulated protein 78 (GRP78), a marker of ER stress, is up-regulated in both cerebral cortical and hippocampal neurons during cerebral infarction. This result suggests that the fragmentation of caspase-12 and the subsequent nuclear translocation of these fragments are involved in the brain infarction process in rats.

Background: Acute cerebral ischemia is caused by different pathophysiological mechanisms. The role of platelets and other blood cells can be different among the stroke subtypes., Methods: Seventy-two patients with acute ischemic cerebrovascular disease, including 31 patients with large vessel disease, 21 patients with cardioembolic disease, and 20 patients with small vessel disease, were evaluated. P-selectin (CD62P) expression and platelet leukocyte aggregates were measured with flow cytometry at the acute phase after the ischemic event. Markers were also measured in 37 control subjects. In all subjects, the serum high-sensitivity C-reactive protein (CRP) was also measured., Results: The platelet-monocyte aggregates (PMA) and platelet-granulocyte aggregates (PGA) in the large vessel disease group were higher than in control group (P=0.002, and P<0.0001, respectively). The PMA and PGA in the small vessel disease group were also higher than in the control group (P=0.004 and P<0.0001, respectively). In contrast, in the cardioembolic disease group, the PMA and PGA were not significantly different from the control group. CD62P expression was higher in all of the patient groups relative to the control group (P<0.05 for all comparisons). Serum CRP levels were also higher in all of the patient groups than in the control group (P<0.0001 for all comparisons)., Conclusions: In contrast to large vessel and small vessel disease, it seems that platelet-leukocyte association does not play a crucial role in the pathogenesis of cardioembolic stroke., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Coronary angiography (CAG) is an invasive diagnostic procedure, which could lead to procedure related complications. One of the well known post-procedural complications is cerebral embolic infarction with or without symptoms. Silent embolic cerebral infarction (SECI) has clinical significance because it can progress to a decline in cognitive function and increase the risk of dementia in the long term. The aim of this study was to detect the incidence and predictors of SECI after diagnostic CAG using diffusion-weighted magnetic resonance imaging (DW-MRI)., Methods: A total of 197 patients with coronary artery disease who underwent DW-MRI for evaluation of intracranial vasculopathy before coronary artery bypass graft surgery were retrospectively enrolled in the present study. DW-MRI was performed within 48 h after diagnostic CAG. SECI was diagnosed as presence of focal bright high signal intensity in DW-MRI. Patients were divided into groups according to presence/absence of SECI (+ SECI vs. - SECI, respectively). The clinical and angiographic characteristics were analyzed and independent predictors were evaluated., Results: Of the 197 patients, SECI occurred in 20 patients (10.2%) after diagnostic CAG. Age, female gender, frequency of underlying atrial fibrillation, extent of coronary disease, and fluoroscopic time during diagnostic CAG were not different between the + SECI and - SECI groups. Left ventricular ejection fraction was significantly lower in the + SECI group than in the - SECI group (45.9 ± 8.5% vs. 51.4 ± 13.1%, p=0.014) and performance rate of internal mammary artery (IMA) angiography was significantly higher in the + SECI group compared with the - SECI group (85% vs. 37.2%, p<0.001). By multivariate analysis, performing IMA angiography was the only predictor of SECI (OR=14.642; 95% CI=3.201 to 66.980, p=0.001)., Conclusions: The incidence of SECI after diagnostic CAG was not infrequent. Diagnostic CAG with IMA angiography may increase the risk of SECI., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: Thrombolysis therapy using tissue-type plasminogen activator (t-PA) is occasionally accompanied by harmful outcomes, including intracerebral hemorrhage. We have reported that Stachybotrys microspora triprenyl phenol-7 (SMTP-7), a candidate thrombolytic drug, has excellent therapeutic effect on cerebral infarction in embolic stroke model in mice; however, little is known regarding whether this agent influences cerebrovascular inflammation following thrombolytic reperfusion. The current study aimed to compare the effects of recombinant t-PA (rt-PA) and SMTP-7 on cerebrovascular inflammation., Methods: The impact of rt-PA- and SMTP-7-induced thrombolytic reperfusion on leukocyte dynamics was investigated in a photochemically induced thrombotic middle cerebral artery occlusion (tMCAo) model in mice., Results: Both rt-PA and SMTP-7 administration in tMCAo mice (each 10 mg/kg) resulted in thrombolytic reperfusion. The SMTP-7-administered mice showed relatively mild rolling and attachment of leukocytes to the vascular wall in the middle cerebral vein, with weak peroxynitrite reactions and proinflammatory gene expression (IL-1β, TNF-α, ICAM-1, and VCAM-1); thus, a small infarct volume compared with rt-PA-administered mice. In vitro study suggested that rt-PA at 20 μg/mL, but not SMTP-7 at a similar concentration, promotes cytokine-induced reactive oxygen species generation in cultured endothelial cells; moreover, SMTP-7 suppressed cytokine-induced VCAM-1 induction in the cells and leukocyte/ endothelial cell adhesions., Conclusions: Relatively mild cerebrovascular inflammation and cerebral infarction in the SMTP-7 mice, compared with in rt-PA mice, is thought to be caused at least in part by direct antioxidative actions of SMTP-7 in ECs.

Background: Much of the brain is perfused by penetrating arteries that are the "single source" of blood to their surrounding tissues. These tissues should be equally vulnerable to ischemia from embolic occlusion, but there are questions about whether emboli have access to the penetrating arteries serving the deep brain tissues. To examine this issue in humans we recorded the number and distribution of new ischemic lesions on diffusion-weighted magnetic resonance imaging (DWMRI) after carotid artery stenting (CAS), a procedure producing showers of numerous small atheroemboli., Methods: Twenty-nine men (aged 62-81) underwent 30 CAS procedures with distal protection in place, and DWMRI 48 hours after the procedure documented new lesions had developed. Thirteen patients were asymptomatic, and 16 had experienced recent symptoms ipsilateral to the treated carotid stenosis. A DWMRI study was done in each patient ≤72 hours before the procedure. All MRI studies were read by the same neuroradiologist., Results: One patient sustained a minor stroke, which resolved. DWNRI found 131 new lesions (median, 3; range, 1-17; interquartile range, 2-4). Lesion size was <5 mm in 96.6% and 5 to 10 mm in 3.1%. Lesions were ipsilateral in 83.1% and contralateral in 16.9%. Lesions were in the distribution of the middle cerebral artery (91.6%), posterior cerebral artery (6.1%), and superior cerebellar artery subclavian artery (2.0%). Most lesions were in the cortex but at a depth where they were best described as cortical/subcortical (90.8%). The rest were in the periventricular white matter (6.1%) and deep gray matter (3.0%)., Conclusions: The ischemic areas developing after CAS were predominately in the deeper layers of the cortex in the distribution of the middle cerebral artery, but lesions were seen throughout the brain. The distribution of lesions caused by CAS-induced embolization coincided with estimates of blood flow to the respective areas of the brain. These data add to the evidence implicating microemboli in ischemic pathologies throughout the brain., (Published by Mosby, Inc.)

The right-to-left shunts (RLS) and white matter lesions (WMLs) are frequently observed in migraineurs and in patients with ischemic stroke. Previous studies have reported that the burden of WMLs did not increase with the intracardiac right-to-left shunt (RLS) in migraineurs. However, some types of WMLs are known to be associated with RLS in patients with stroke and dementia. The aim of the study was to demonstrate the difference in the size and location of WMLs, according to the existence of RLS in patients with headache. From the prospective headache registry, a total of 425 subjects (age, 30.8 ± 5.1 years; 303 women; 242 migraineurs; 183 patients with tension-type headache (TTH)) were retrospectively reviewed and evaluated for RLS and WMLs using M-mode power transcranial Doppler sonography (mTCD) and brain magnetic resonance imaging scans. We scored WMLs, according to the Rotterdam Scan Study, and assessed the association between RLS presence and the location and size of WMLs. The number of small deep WMLs (dWMLs) and the prevalence of RLS, defined as microembolic signals (MES) ≥ 11, were higher in patients with migraine (small dWMLs, 6.23 vs. 4.05; RLS, 36.8% vs. 10.9%), compared to patients with TTH. There was no significant difference in the sum of periventricular WML grades or the total volume of dWMLs between TTH and migraine patients. Among the migraineurs, the patients with RLS more frequently had small dWMLs, aura, and heart disease compared to those without RLS. In addition, RLS were also independent predictors for the presence of small dWMLs from the multivariate binary regression analysis (p < 0.01; OR = 3.24; 95%CI 1.56-6.72). Small dWMLs are associated with RLS in young migraineurs. These results imply that paradoxical embolism may cause the small WMLs in some migraineurs.

This review discusses the pathological changes in the heart and vessels underlying brain ischaemic injury, with a major focus on atherosclerotic disease of the brain induced by lesions of the extracranial cervical and major intracranial arteries and small-vessel disease of the brain. The carotid bifurcation is the primary site for atherosclerotic changes, for which extensive clinical trials and pathological analyses on carotid endarterectomy specimens have been performed. Plaque rupture and erosion give rise to thrombus formation, which leads to brain ischaemic injury. These changes have much in common with atherosclerotic lesions of the subepicardial coronary arteries. Emboli of various types of particles are characteristics of brain ischaemic injury. Thrombi rich in fibrin and red blood cells (red thrombi) that develop in the cardiac chambers are common sources of cerebral emboli. Small-vessel disease of the brain induces fibrinoid necrosis, microaneurysm, fibrohyalinosis, lipohyalinosis and microatheroma, changes commonly associated with hypertension. The acute hypertensive small-vessel changes organize to create segmental arterial disorganization and deep small infarcts when they escape from rupture. Some specific vascular diseases responsible for brain ischaemic injury are briefly reviewed also., (© 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.)

This review of age-related brain microvascular pathologies focuses on topics studied by this laboratory, including anatomy of the blood supply, tortuous vessels, venous collagenosis, capillary remnants, vascular density and microembolic brain injury. Our studies feature thick sections, large blocks embedded in celloidin, and vascular staining by alkaline phosphatase. This permits study of the vascular network in three dimensions, and the differentiation of afferent from efferent vessels. Current evidence suggests that there is decreased vascular density in ageing, Alzheimer's disease and leukoaraiosis, and cerebrovascular dysfunction precedes and accompanies cognitive dysfunction and neurodegeneration. A decline in cerebrovascular angiogenesis may inhibit recovery from hypoxia-induced capillary loss. Cerebral blood flow is inhibited by tortuous arterioles and deposition of excessive collagen in veins and venules. Misery perfusion due to capillary loss appears to occur before cell loss in leukoaraiosis, and cerebral blood flow is also reduced in the normal-appearing white matter. Hypoperfusion occurs early in Alzheimer's disease, inducing white matter lesions and correlating with dementia. In vascular dementia, cholinergic reductions are correlated with cognitive impairment, and cholinesterase inhibitors have some benefit. Most lipid microemboli from cardiac surgery pass through the brain in a few days, but some remain for weeks. They can cause what appears to be a type of vascular dementia years after surgery. Donepezil has shown some benefit. Emboli, such as clots, cholesterol crystals and microspheres can be extruded through the walls of cerebral vessels, but there is no evidence yet that lipid emboli undergo such extravasation., (© 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.)

Background and Purpose: thrombolytic treatment with tissue plasminogen activator (tPA) improves outcome of patients with stroke who can be treated within 3 hours of symptom onset. However, delayed treatment with tPA leads to increased risk of hemorrhagic transformation and can result in enhanced brain injury. The purpose of this study is to validate a reproducible mouse model of hemorrhagic transformation associated with delayed administration of tPA., Methods: mice were anesthetized and thrombin was injected into the middle cerebral artery to induce the formation of a clot as described by Orset et al. To induce reperfusion, tPA (10 mg/kg) was intravenously administered 20 minutes or 3 hours after thrombin injection., Results: thrombin produced a clot in 83.1% of the animals, which caused focal ischemia determined 24 hours after the injection. Different degrees of bleeding were found in the middle cerebral artery occlusion group, including hemorrhagic infarction type 1 (HI-1) in 46.2%, hemorrhagic infarction type 2 (HI-2) in 30.8% and parenchymal hemorrhage type 1 in 23.0%. Administration of tPA 20 minutes after the occlusion produced an effective reperfusion in 62.5% of the animals and reduced both infarct volume and appearance of severe hemorrhage (10% nonhemorrhage, 80% HI-1 and 10% HI-2). However, administration of tPA 3 hours after the occlusion led to effective reperfusion in 47.1% of the animals, did not reduce infarct volume, caused hemorrhagic transformation (25% HI-1, 37.5% HI-2, and 37.5% parenchymal hemorrhage type 1), and increased hemorrhage and brain swelling., Conclusions: we have set up a reproducible mouse model of hemorrhagic transformation associated with delayed administration of tPA similar to that observed in humans.

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.)

Cardiac tumor is a rare, but clinically important source of cerebral embolism. We report a case of metastatic chondrosarcoma in the left atrium with multiple cerebral emboli. A computed tomography scan of the chest revealed a large mass in the left atrium and pulmonary vein. The patient underwent heart surgery to remove the metastatic chondrosarcoma in the left atrium, to prevent the formation of further systemic emboli and possible sudden death. The cardiac tumor resection was successful, and the patient was discharged from the hospital without any handicap. This is a rare case of metastatic cardiac tumor that was a source of emboli into the brain and was eradicated., (Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

To clarify the mechanism of the development of cerebral infarcts in the internal carotid artery (ICA) dissection, the data of neuroimaging (localization of infarcts) and angiography have been analyzed in 49 patients (19 females 30 males, mean age 35,6 +/- 11,3 years). Four variants of infarct localization have been distinguished: 1 - the whole ICA territory (middle and anterior cerebral arteries - MCA, ACA) - 10%, 2 - the territory of superficial and deep branches of MCA- 37%, 3- the territory of superficial MCA branches and cortical-medullar arteries - 31% (the cortex and underlying white matter - 19%, the periventricular white matter and semiovale center - 6%, combined localization - 6%); 4 - the territory of deep (perforating) MCA branches (the basal ganglia and adjacent white matter) - 22%. In most of patients (92%) the dissection resulted in the occlusion or severe stenosis of intracranial ICA which in a half of cases extended to MCA and/or ACA. In 72% patients dissection involved the extracranial ICA. The marked obstructive process in the dissected ICA allows to assume that the hemodynamic, but not embolic, mechanism plays a key role in the development of infarcts. This is in line with the frequent infarct localization in the end or border zones (superficial and deep) of brain blood supply (31%) and the development of stroke during a sleep (49%). Arterio-arterial embolism as a mechanism of ischemic stroke development was found in 8% of patients with the isolated extracranial ICA dissection. It caused stenosis of the lumenand in 6% accompanied by the pseudoaneurism formation. Thrombi formed inside the aneurism could be the origin of the embolism.

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.)

Objective: To study the correlation of compensation by collateral circulation and clinical locations in ischemic stroke cases., Methods: A total of 25 ischemic stroke cases were retrospectively analyzed. MRI (magnetic resonance imaging) and DSA (digital subtraction angiography) were performed in all cases. Each patient was found to have at least one cerebral artery occlusion by DSA. The quantity relationship between collateral circulation and ischemic stroke location was analyzed by SPSS 11.5 statistics software., Results: Among all cases, 46 arterial occlusions were found by chance. DSA demonstrated internal carotid artery occlusion (n = 24) and vertebral & basilar artery occlusion (n = 22). And all cases had at least one collateral circulation. Among 23 cases of single collateral circulation, there were 8 cases of single ischemic stroke locations and 15 cases of multiple ischemic stroke locations; among 23 cases of multiple collateral circulations, there were 18 cases of single ischemic stroke locations and 5 cases of multiple ischemic stroke locations., Conclusion: Effective collateral circulation can be established spontaneously through multiple ways when cerebral artery occlusion takes place if an intact Wills circle is present. Multiple collateral circulations may significantly decrease the quantity of ischemic stroke locations.

Using magnetic resonance imaging (MRI) protocols of T(2)-, T(2)*-, diffusion- and susceptibility-weighted imaging (T2WI, T2*WI, DWI, and SWI, respectively) with a 7T system, we tested the hypothesis that treatment of embolic stroke with erythropoietin (EPO) initiated at 24 hr and administered daily for 7 days after stroke onset has benefit in repairing ischemic cerebral tissue. Adult Wistar rats were subjected to embolic stroke by means of middle cerebral artery occlusion (MCAO) and were randomly assigned to a treatment (n = 11) or a control (n = 11) group. The treated group was given EPO intraperitoneally at a dose of 5,000 IU/kg daily for 7 days starting 24 hr after MCAO. Controls were given an equal volume of saline. MRI was performed at 24 hr and then weekly for 6 weeks. MRI and histological measurements were compared between groups. Serial T2WI demonstrated that expansion of the ipsilateral ventricle was significantly reduced in the EPO-treated rats. The volume ratio of ipsilateral parenchymal tissue relative to the contralateral hemisphere was significantly increased after EPO treatment compared with control animals, indicating that EPO significantly reduces atrophy of the ipsilateral hemisphere, although no significant differences in ischemic lesion volume were observed between the two groups. Angiogenesis and white matter remodeling were significantly increased and occurred earlier in EPO-treated animals than in the controls, as evident from T2*WI and diffusion anisotropy maps, respectively. These data indicate that EPO treatment initiated 24 hr poststroke promotes angiogenesis and axonal remodeling in the ischemic boundary, which may potentially reduce atrophy of the ipsilateral hemisphere., (© 2010 Wiley-Liss, Inc.)

Objective: Previous studies have investigated the predictive value of clinical and morphologic parameters for distal embolization during carotid interventions. The composition of the atherosclerotic plaque, using virtual histology intravascular ultrasound (VH-IVUS) imaging obtained with an IVUS catheter that is advanced through the lesion after a filter has been placed distally, has not been evaluated as a marker for cerebral embolization. The purpose of this study was to assess the relationship between atherosclerotic plaque composition determined with VH-IVUS and the occurrence of cerebral embolization after carotid artery stenting (CAS)., Methods: During a 10-month period, 24 patients undergoing CAS procedures using a filter device for embolic protection were prospectively evaluated. All patients underwent VH-IVUS exams at the time of the intervention, transcranial Doppler (TCD) monitoring during CAS, and pre- and 24-hour postprocedural diffusion-weighted magnetic resonance imaging (DW-MRI) exams. Using VH-IVUS, plaque components were characterized as fibrotic, fibrofatty, dense calcium, and necrotic core. The frequency of Doppler-detected microembolic signals (MES) during CAS and the incidence and location of acute postprocedural embolic lesions detected with DW-MRI were assessed to determine cerebral embolization. Univariate and correlation analyses were used to assess the association between plaque composition and frequency of cerebral embolization., Results: No periprocedural transient ischemic attacks, strokes, or deaths occurred within 30 days. Seventeen patients (71%) demonstrated new acute cerebral emboli in DW-MRI. Of these, all revealed ipsilateral lesions and 12 (50%) had contralateral lesions. For the entire study group, the median number of ipsilateral DW-MRI lesions was 1 (range, 0 to 3), and TCD MES counts were 227 (interquartile range, 143-315). Volumetric VH-IVUS analysis revealed that there was a trend for larger median dense calcium volume in patients with ipsilateral subclinical cerebral embolism detected with DW-MRI (33.2±24.5 mm3 vs 11.4±6.1 mm3; P=.08). Scatter plots of plaque components revealed statistically significant correlation between fibrofatty plaque volume (Spearman r=0.49; P=.016) and number of new ipsilateral lesions in DW-MRI. Degree of cerebral embolization during CAS measured with TCD correlated with plaque burden, necrotic core, fibrofatty, and fibrous volumes., Conclusions: Plaque composition, as determined by VH-IVUS, only weakly correlates with the degree of cerebral embolization after carotid stenting. Specifically, there is a trend for larger dense calcium volume in patients with distal embolization. Of note, the proportion of necrotic core, which has traditionally been considered the main component of a vulnerable or unstable plaque, is not definitely associated with subclinical cerebral embolization after CAS when a filter device for embolic protection is used. The role of VH-IVUS in evaluating plaque composition during CAS remains unestablished and warrants further investigation., (Published by Mosby, Inc.)

Background: Radiofrequency left atrial catheter ablation has become a routine procedure for treatment of atrial fibrillation. The aim of this study was to assess with preprocedural and postprocedural cerebral magnetic resonance imaging the thromboembolic risk, either silent or clinically manifest, in the context of atrial fibrillation ablation. The secondary end point was the identification of clinical or procedural parameters that correlate with cerebral embolism., Methods and Results: A total of 232 consecutive patients with paroxysmal or persistent atrial fibrillation who were candidates for radiofrequency left atrial catheter ablation were included in the study. Pulmonary vein isolation or pulmonary vein isolation plus linear lesions plus atrial defragmentation with the use of irrigated-tip ablation catheters was performed. All of the patients underwent preprocedural and postablation cerebral magnetic resonance imaging. A periprocedural symptomatic cerebrovascular accident occurred in 1 patient (0.4). Postprocedural cerebral magnetic resonance imaging was positive for new embolic lesions in 33 patients (14). No clinical parameters such as age, hypertension, diabetes mellitus, previous history of stroke, type of atrial fibrillation, and preablation antithrombotic treatment showed significant correlation with ischemic cerebral embolism. Procedural parameters such as activated clotting time value and, in particular, electric or pharmacological cardioversion to sinus rhythm correlated with an increased incidence of cerebral embolism. Cardioversion was also associated with an increased risk of 2.75 (95 confidence interval, 1.29 to 5.89; P=0.009)., Conclusions: Radiofrequency left atrial catheter ablation carries a low risk of symptomatic cerebral ischemia but is associated with a substantial risk of silent cerebral ischemia detected on magnetic resonance imaging. Independent risk factors for cerebral thromboembolism are the level of activated clotting time and, in particular, the electric or pharmacological cardioversion to sinus rhythm during the procedure.

Gardnerella vaginalis is typically associated with bacterial vaginosis in women. However, balanitis, urethritis, urinary tract infections and asymptomatic bacteraemia have also been described in men. Here we report a case of G. vaginalis septicaemia with infective endocarditis and septic emboli in the kidney and brain of an adult male.

Background: Cerebral ischemia in patients with carotid artery atherosclerosis is most often caused by thromboembolism, while hemodynamic stroke mechanism is rare. Differences in plaque inflammation according to stroke mechanism are an understudied issue. The purpose of this pilot study was to compare carotid plaque inflammation in patients with thromboembolic and hemodynamic cerebral ischemia., Methods: We included 6 patients with hemodynamic and 27 with embolic cerebral ischemia who had carotid endarterectomy (CEA). We compared plaque morphology markers (macrophages, T cells, MMP-9, plaque rupture, surface thrombus, intraplaque hemorrhage, lipid core) between patients with hemodynamic and embolic cerebral ischemia and assessed vascular events and deaths during the first year post CEA., Results: Compared to patients with hemodynamic mechanism, those with embolic mechanism showed a higher median (interquartile range) content of T cells/mm(2) [49.66 (21.26-71.39) vs. 10.28 (7.05-13.87); P=0.0005] and higher median total percentages of macrophage area [2.81% (1.69-4.09) vs. 0.99% (0.57-1.50); P=0.003] and MMP-9 area [0.63% (0.42-1.01) vs. 0.25% (0.05-0.45); P=0.007]. Signs of plaque instability such as plaque rupture, surface thrombus and intraplaque hemorrhage showed a tendency to be more pronounced in patients with thromboembolism. The incidences of vascular events and the survival rates in the first year after CEA were similar in the two groups., Conclusions: Major differences in plaques related to stroke mechanism were found in patients with symptomatic carotid stenosis. However, further investigations are necessary to validate our results. Identification of stroke mechanism may improve risk stratification and could help to identify the most suitable secondary stroke prevention strategy., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

This review encourages the reader to consider cerebral vascular disease beyond the traditional clinical end points of major motor and speech strokes and to consider the possible impact of embolic cerebral vascular disease on vascular cognitive decline. This article examines the issue of "silent" strokes in the relationship between the structural stability of atherosclerotic carotid plaque and the development of nonmotor symptomatology, including cognitive decline. It addresses the question of the role of carotid emboli in silent stroke and their cognitive sequelae. In a study of endarterectomy patients, we relate plaque elasticity and its development of mechanical strain features and thinning of stabilizing fibrous cap at the point of these mechanical strain features. The possibility that microemboli from such mechanically unstable carotid plaques could contribute to silent strokes led to a study of cognitive function in such patients. A linear relationship between the process of mechanically unstable areas of carotid plaques and cognitive decline suggests a contributory role for such a process in silent strokes.

Objective: It has been reported that embolic signal (ES) detected by transcranial Doppler (TCD) has clinical significance, especially in patients with recent stroke attributable to arterial or cardiac embolism. Therefore, we conducted this study to determine whether the prevalence of ES is high in ischemic stroke patients with cancer and related to hypercoagulopathy., Methods: We prospectively studied cancer patients with acute ischemic stroke within the middle cerebral artery (MCA) distribution on diffusion-weighted imaging. Conventional stroke mechanisms (CSMs) were determined using cardiologic and vascular studies. Additionally, the coagulation status was assessed based on the serum D-dimer levels, and TCD monitoring was performed on both MCAs for 30 minutes to detect ES. Clinical features including vascular risk factors, characteristics of ischemic stroke, and cancer and laboratory findings associated with the presence of ES were evaluated., Results: A total of 74 patients were finally included in this study. ES was more commonly observed in patients without CSMs (22 of 38 patients, 57.9%) than in those with CSMs (12 of 36 patients, 33.3%) (p = 0.034). Moreover, ES was more commonly detected in patients with high D-dimer levels (p < 0.001), and D-dimer levels were significantly correlated with the number of ESs in patients without CSMs (r = 0.732, p < 0.001), but were poorly correlated in patients with CSMs (r = 0.152, p = 0.375). Higher levels of D-dimer (odds ratio [OR], 1.082 per 1 microg/ml increase; 95% confidence interval [CI], 1.014-1.154) and adenocarcinoma (OR, 3.829; 95% CI, 1.23-13.052) were independently associated with the presence of ES. The use of anticoagulants dramatically decreased the D-dimer levels., Interpretation: A high prevalence of ES was observed in cancer patients with ischemic stroke, especially in those without CSMs. Elevated D-dimer levels were independently associated with ES, and decreased dramatically with the use of anticoagulants. ANN NEUROL 2010;68:213-219.

Background and Purpose: Watershed ischemia is a significant cause of stroke in severe carotid disease, but its pathophysiology is unsettled. Although hemodynamic compromise has long been regarded as the main mechanism-particularly with deep watershed infarction-there is some contradictory evidence from clinical and pathological studies for a role of microembolism, thought to result from plaque inflammation. However, no study so far has directly addressed these conflicting scenarios., Methods: In 16 consecutive patients with recent transient ischemic attack/minor stroke and ipsilateral 50% to 99% carotid stenosis, we prospectively obtained (1) plaque inflammation mapping with (18)F fluorodeoxyglucose positron emission tomography; (2) brain MRI and perfusion MR; and (3) transcranial Doppler detection of microembolic signals (MES). Patients were excluded if on dual antiplatelets or with a potential cardiac source of emboli or contralateral MES., Results: We found the expected significant relationship between (1) degree of stenosis and severity of distal hemodynamic impairment in the watershed areas; and (2) degree of in vivo plaque inflammation and rate of MES/hr. Deep watershed infarcts were present in 8 patients and MES in 8 (3 with both). There was no systematic association between the presence of deep watershed infarcts and either hemodynamic impairment or MES, but deep watershed infarcts were present only when either hemodynamic impairment or MES was present (P=0.01)., Conclusions: This pilot study supports the idea that in symptomatic carotid disease, deep watershed infarcts result either from hemodynamic impairment secondary to severe lumen stenosis or from microembolism secondary to plaque inflammation. There was no direct evidence that both mechanisms act in synergy.

Background and Purpose: High-density lipoprotein (HDL) levels are inversely associated with stroke incidence, suggesting a protective effect. Using a rat model, we tested the hypothesis that HDL exerts direct vasculo-/neuroprotective effects when administered during the acute phase of embolic stroke., Methods: After embolic occlusion, Sprague-Dawley rats were randomly treated intravenously with purified HDL versus saline immediately (2, 10 mg/kg) or 3 or 5 hours (10 mg/kg) after stroke. The effects of HDL were assessed blindly 24 hours later by evaluating neurological deficit score and measuring the infarct volume and blood-brain barrier breakdown. Protease activities and neutrophil infiltration were also evaluated., Results: HDL injection immediately after stroke (10 mg/kg) reduced by 68% the mortality at 24 hours (P=0.015). HDL administration immediately or at 3 or 5 hours after stroke also reduced cerebral infarct volume by 74%, 68%, and 70.7%, respectively (P=0.0003, P=0.011, and P=0.019; n=17 per group). The neurological deficit at 24 hours in the HDL-treated group was decreased versus the saline-treated group (P=0.015). Ischemia-induced blood-brain barrier breakdown was significantly reduced in HDL-treated rats versus controls (P=0.0045). Neuroprotective effects of HDL were associated with decreased neutrophil recruitment in the infarct area (P=0.0027) accompanied by reduced matrix metalloproteinase gelatinase activity. Immunostaining showed that HDL was associated with endothelial and glial cells, and also that intercellular adhesion molecule-1 expression was decreased in vessels within the infarct area., Conclusions: Administration of HDL is neuroprotective when performed up to 5 hours after experimental stroke. This effect may be attributed to the ability of HDL to protect the blood-brain barrier and limit neutrophil recruitment.

Subtle cerebral air microembolisation (CAM) is a typical complication of various medical interventions such as open heart surgery or angiography and can cause transient or permanent neurological and neuropsychological deficits. Evaluation of the underlying pathophysiology requires animal models that allow embolisation of air bubbles of defined diameter and number. Herein we present a method for the production of gas bubbles of defined diameter and their injection into the carotid artery of rats. The number of gas microemboli injected is quantified digitally using a high speed optical image capturing system and a custom-made software. In a first pilot study, 0, 50, 100, 400 and 800 gas bubbles of 160 microm in diameter were injected into the carotid artery of rats. Offline evaluation revealed a high constancy of the bubble diameters (mean 159.95+/-9.25 microm, range 144-188 microm) and the number of bubbles injected. First preliminary data indicate that with increasing number of bubbles embolised, more animals revealed neurological deficits and (particularly with higher bubble counts) brain infarctions on TTC-staining. Interestingly, also animals without overt infarcts on TTC-staining displayed neurological deficits in an apparently dose dependent fashion, indicating subtle brain damage by air embolism. In conclusion, the method presented allows injecting air bubbles of defined number and diameter into cerebral arteries of rats. This technique facilitates animal research in the field of air embolisation., (Copyright 2010 Elsevier B.V. All rights reserved.)

Background and Purpose: Patent foramen ovale (PFO) can be diagnosed by contrast-enhanced transcranial Doppler (cTCD), but no definitive criteria exist to correlate the results obtained from cTCD with diagnoses of PFO obtained by contrast-enhanced transesophageal echocardiography (cTEE). The aim of the present study was to analyze markers in the positive RLS by cTCD that confirm the PFO by cTEE., Methods: Twenty-six stroke patients who had previously submitted to cTEE, 16 with PFO (PFO group) and 10 without PFO (no-PFO group), were evaluated for three markers based on a positive cTCD test. The number of microembolic signs (MES), the latency time (LT) to the first MES and the duration time (DT) of MES were evaluated to look for a difference between the PFO and no-PFO group., Results: The PFO group had higher MES (80.9+/-124.5 vs. 10.2+/-25.6, p<0.001), shorter LT (12.5+/-6.6 vs. 16.2+/-5.1, p=0.02) and longer DT (21.4+/-17.4 vs. 11.7+/-12.5, p=0.013) compared with the no-PFO group. Considering only MCA tests with more than 9 MES and LT shorter than 9s, 30% of patients from the PFO group had positive tests compared with no patients from the no-PFO group. This cutoff demonstrates a specificity and positive predictive value of 100%., Conclusions: The rule of nine (>9 MES and LT <9s) for cTCD can be considered a marker for PFO diagnosis by cTEE., (Copyright 2010. Published by Elsevier B.V.)

Background and Purpose: To investigate the incidence of retrograde flow from complex plaques (> or =4-mm-thick, ulcerated, or superimposed thrombi) of the descending aorta (DAo) and its potential role in embolic stroke., Methods: Ninety-four consecutive acute stroke patients with aortic plaques > or =3-mm-thick in transesophageal echocardiography were prospectively included. MRI was performed to localize complex plaques and to measure time-resolved 3-dimensional blood flow within the aorta. Three-dimensional visualization was used to evaluate if diastolic retrograde flow connected plaque location with the outlet of the left subclavian artery, left common carotid artery, or brachiocephalic trunk. Complex DAo plaques were considered an embolic source if retrograde flow reached a supra-aortic vessel that supplied the territory of visible acute and embolic retinal or cerebral infarction., Results: Only decreasing heart rate was correlated (P<0.02) with increasing flow reversal to the aortic arch. Retrograde flow from complex DAo plaques reached the left subclavian artery in 55 (58.5%), the left common carotid artery in 23 (24.5%), and the brachiocephalic trunk in 13 patients (13.8%). Based on routine diagnostics and MRI of the ascending aorta/aortic arch, stroke etiology was determined in 57 and cryptogenic in 37 patients. Potential embolization from DAo plaques was then identified in 19 of 57 patients (33.3%) with determined and in 9 of 37 patients (24.3%) with cryptogenic stroke., Conclusions: Retrograde flow from complex DAo plaques was frequent in both determined and cryptogenic stroke and could explain embolism to all brain territories. These findings suggest that complex DAo plaques should be considered a new source of stroke.

Background and Purpose: Treatment with a selective proteasome inhibitor, VELCADE, in combination with tissue plasminogen activator (tPA) extended the therapeutic window to 6 hours in young rats after stroke. However, stroke is a major cause of death and disability in the elderly. The present study investigated the effect of VELCADE in combination with a low-dose tPA on aged rats after embolic stroke., Methods: Male Wistar rats at the age of 18 to 20 months were treated with VELCADE (0.2 mg/kg) alone, a low-dose tPA (5 mg/kg) alone, combination of VELCADE and tPA, or saline 2 hours after embolic middle cerebral artery occlusion. To test the contribution of endothelial nitric oxide synthase to VELCADE-mediated neuroprotection, endothelial nitric oxide synthase knockout and wild-type mice were treated with VELCADE (0.5 mg/kg) 2 hours after embolic stroke., Results: Treatment with VELCADE significantly reduced infarct volume, whereas tPA alone did not reduce infarct volume and aggravated blood-brain barrier disruption in aged rats compared with saline-treated rats. However, the combination treatment significantly enhanced the reduction of infarct volume, which was associated with an increase in endothelial nitric oxide synthase activity compared with saline-treated rats. Additionally, the combination treatment promoted thrombolysis and did not increase the incidence of hemorrhage transformation. VELCADE significantly reduced lesion volume in wild-type mice but failed to significantly reduce lesion volume in endothelial nitric oxide synthase knockout mice., Conclusions: Treatment with VELCADE exerts a neuroprotective effect in aged rats after stroke. The combination of VELCADE with the low-dose tPA further amplifies the neuroprotective effect. Endothelial nitric oxide synthase at least partly contributes to VELCADE-mediated neuroprotection after stroke.

Background: A substantial proportion of ischemic strokes have an embolic mechanism, but the source of embolism is not detected. Coexistence of subdiaphragmatic visceral infarction (SDVI; e.g., renal, splenic, hepatic, bowel infarction) may be a suggestion of a common source of embolism. One large autopsy study found SDVI in 21.5% of patients with fatal stroke., Method: We performed diffusion-weighted magnetic resonance abdominal imaging and subsequently performed it in consecutive patients with stroke or TIA and a history of nonvalvular atrial fibrillation., Results: Among 27 patients, 6 had SDVI (3 recent renal, 1 recent splenic, and 3 old splenic infarction). The median time between onset of ischemic stroke and abdominal MRI was 8 days (interquartile range 3-15 days). No predictive factor of SDVI was found in this study population with respect to demographic or ultrasound characteristics., Conclusions: One in 5 patients with nonfatal cardioembolic stroke or TIA may be associated with subdiaphragmatic visceral infarction (SDVI). Further study should evaluate the frequency of SDVI in patients with stroke of unknown cause.

We report a case of intracerebral air embolism after cardiopulmonary resuscitation in a patient with a fatal myocardial infarct. Cases of cerebral air embolism rarely occur as a result of cardiopulmonary resuscitation in cases of cardiopulmonary arrest on arrival. This is the first case with postmortem histological confirmation.

Cerebral lipiodol embolism (CLE) is an extremely rare complication of transcatheter arterial chemoembolization for hepatocellular carcinoma (HCC). The authors present a case of CLE that occurred after the second hepatic arterial chemoembolization for HCC, and attempt to introduce several plausible mechanisms of CLE, after reporting the clinical and radiological findings and reviewing the medical literature.