Case Report: Postmortem brain and heart pathology unveiling the pathogenesis of coexisting acute ischemic stroke and electrocardiographic abnormality.

Electrocardiography abnormalities have been occasionally reported at the onset of stroke. Simultaneous electrocardiographic abnormalities and stroke require a rapid differentiated diagnosis among several diseases. However, direct causal relationships remain unclear. A 92-year-old woman presented to our emergency department in a sudden-onset coma. The patient suffered from huge acute ischemic stroke with bilateral internal carotid artery occlusion assessed by brain magnetic resonance imaging, and her electrocardiography showed ST-segment elevation at II, III, aVF and V4-6, and atrial fibrillation (AF). However, the etiology of the medical condition was clinically unknown. Eventually, the patient died on day 4 of hospitalization before the diagnosis could be completed. Therefore, an autopsy was performed to investigate pathological findings after obtaining informed consent from the family. A postmortem pathological evaluation demonstrated that fibrin mural thrombi in the left atrial appendage (LAA), and the cerebral and coronary arteries possessed CD31-positive endothelial cells, and CD68-positive and CD168-positive macrophages in a similar fashion, suggesting the fibrin thrombi observed in the three sites implicated to be identical. We concluded that nearly concurrent cerebral and coronary artery embolism because of the fibrin thrombi in LAA developed by AF. Simultaneous cerebral infarction and myocardial infarction are referred to as cardiocerebral infarction (CCI), a rare disorder for which clear pathomechanisms remain unknown, although several mechanisms of CCI have been proposed. We first revealed the clear pathology of CCI using the autopsy. Additional pathological studies are warranted to establish clear pathomechanisms and preventive strategies of CCI.

Usefulness of combining CISS and digital subtraction angiography in diagnosis of isolated posterior inferior cerebellar artery dissection.

A 63-year-old man was admitted to our stroke center with brain infarction in the left posterior inferior cerebellar artery (PICA) territory. The initial MRI showed no findings suggestive of arterial dissection, and post-discharge MRI showed no temporal changes. Digital subtraction angiography (DSA) revealed vasodilation of the proximal portion of the PICA but it was uncertain whether dissection was present. Discrepancy between the outer contour seen on constructive interference in steady state (CISS) MRI and the inner contour seen on DSA suggested the presence of intramural hematoma. The patient was diagnosed with brain infarction caused by isolated PICA dissection (iPICAD). Imaging evaluation of combined CISS and DSA may be particularly useful for identification of small iPICAD lesions.

Usefulness of Ultrasonography in the Diagnosis and Follow-up of Extracranial Vertebral Artery Dissection.

Extracranial vertebral artery dissection is a cerebrovascular disease that occurs most commonly in young people. A 32-year-old man experienced sudden cervical pain and was diagnosed with left vertebral artery dissection after arterial changes were identified by ultrasonography. The reduction in the size of an intramural hematoma in the left vertebral artery and in the peak systolic velocity were evaluated over time. Computed tomography, magnetic resonance imaging, and cerebral angiography are generally performed to diagnose and follow-up extracranial vertebral artery dissection; however, carotid ultrasonography has an advantage over these modalities by enabling the simultaneous observation of vascular morphology and hemodynamics.

Impact of blood flow volume in determining the destination of intracardiac thrombi using computational fluid dynamics.

Atrial fibrillation (AF) induces cardioembolic stroke due to intracardiac fibrin thrombus formation. Although it is well established that a cardioembolic stroke affects the anterior circulation more frequently than it affects the posterior circulation, the destination where the thrombi migrate when cardioembolic stroke occurs in each patient remains unclear. We present a critical case wherein a bilateral internal carotid artery (ICA) territory infarction was diagnosed in a patient with AF who apparently developed nearly simultaneous occlusion in the ICAs bilaterally. A 92-year-old woman with AF who appeared to have developed bilateral occluded common carotid artery (CCA)-ICAs almost simultaneously presented after the sudden onset of coma and quadriplegia and was diagnosed with bilateral ICA territory infarction. The patient died at 4 days after the onset due to the huge infarction. The blood flow in the aorta and the major branches of the aortic arch were examined using computational fluid dynamics (CFD) based on contrast-enhanced computed tomography angiography, which revealed that the right and left CCAs covered larger flow volumes than the other aortic arch branches, suggesting that the intracardiac thrombi migrated into the bilateral CCA-ICAs in the patient. The study findings imply that the fluid dynamic factors of major branches from the aortic arch can be one of the decisive factors for intracardiac thrombus distribution. CFD could simulate patient-specific hemodynamics and may be useful to investigate the susceptibility of the aortic arch branches to occlusion by AF-induced intracardiac emboli.

Progressive Small-Vessel Strokes Following Antiretroviral Therapy in a Patient with Acquired Immunodeficiency Syndrome.

We report a case of a 59-year-old man with human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome (AIDS) who developed multiple small-vessel strokes during the immune reconstitution phase. The patient had been diagnosed with HIV/AIDS with a low CD4 count and high viral load and started combinational antiretroviral therapy (cART) with raltegravir, emtricitabine, and tenofovir alafenamide fumarate seven months before the admission. He was admitted to our hospital with complaints of mild dysarthria and left-sided hemiparesis, but lacking consciousness/cognitive disturbances. Diffusion-weighted images (DWI) revealed multiple areas of hyperintensity in the anterior circulation system of the brain. Because we identified decreased activity of protein S through extensive examinations, we treated him initially with intravenous infusion of heparin sodium and aspirin; however, DWI detected multiple progressive small-vessel strokes after that. We considered that the immune reconstitution accounted for the small-vessel vasculopathy/vasculitis, leading to ischemic stroke. Therefore, we initiated oral administration of prednisolone, which successfully prevented stroke recurrence. This report describes a case of multiple small-vessel strokes following cART for AIDS during the immune reconstitution phase, effectively treated with steroids, which may often go undiagnosed due to their relatively mild symptoms.

Concentrations of dabigatran administered after acute ischemic stroke.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate the anticoagulation intensity of dabigatran for acute ischemic stroke patients and hemorrhagic/ischemic events after early initiation of dabigatran. METHODS: Acute ischemic stroke/transient ischemic attack (TIA) patients admitted to our hospital who started dabigatran from January 2012 to December 2017 were studied. Blood samples were drawn just before (0 h) and 4 h after dabigatran at a median of 5 days after starting dabigatran to measure dabigatran concentrations (C0h, C4h) based on the thrombin clotting time assay (Hemoclot®). RESULTS: Of the 70 patients (54 men, 69 ± 9 y), 14 started dabigatran after a TIA, and 56 started it after an ischemic stroke a median of 5 days after onset. C0h, C4h was 82.5 ± 58.0, 143.1 ± 98.2 ng/dl (150 mg BID, 35 patients) and 50.6 ± 40.9, 91.2 ± 64.7 ng/ml (110 mg BID, 35 patients). During a median follow-up of 382 (IQR 109-688) days of all 70 patients, five had clinical events. Three patients had bleeding events, two with nasal bleeding (C0h, C4h: 50, 80 ng/ml, C0h, C4h: 91, 173 ng/ml) and one with GI bleeding (C0h, C4h: 5, 5 ng/ml). Two patients had ischemic events, one with ischemic stroke (C0h, C4h: 10, 50 ng/ml) and another with acute myocardial infarction (C0h, C4h: 40, 40 ng/ml). CONCLUSIONS: There was no obvious relationship between dabigatran concentration and hemorrhagic/ischemic events in this study. Larger sample study will be needed to examine the relationship between the concentration and events in clinical practice.

Usefulness of Transesophageal Echocardiography for Predicting Covert Paroxysmal Atrial Fibrillation in Patients with Embolic Stroke of Undetermined Source.

BACKGROUND: Covert paroxysmal atrial fibrillation (CPAF) is a major cause of embolic stroke of undetermined source (ESUS). However, detecting PAF during hospitalization in these patients is difficult. OBJECTIVES: This study aimed to determine whether findings of transesophageal echocardiography (TEE) during hospitalization are associated with later detection of PAF in patients with ESUS. METHOD: We retrospectively studied 348 patients with ESUS who were admitted to our hospital within 1 week of onset. These patients met the criteria of ESUS, underwent TEE during hospitalization, and were followed up for at least 1 year. RESULTS: We found PAF in 35 (10.0%) patients. In patients with PAF, spontaneous echo contrast (SEC) and low left atrial appendage flow (LAAF) by TEE and enlargement of the left atrial dimension (LAD) by transthoracic echocardiography were identified more frequently compared with those who did not have PAF. In multivariate analysis, SEC and an LAD ≥42 mm were independently associated with later detection of PAF (p < 0.05). An association of LAAF <46.9 cm/s and PAF was marginal (p = 0.09). The specificity of the combined finding of SEC and/or LAAF with that of LAD increased up to 90%, while that of LAD alone was 70%. CONCLUSIONS: The findings of TEE during hospitalization may be useful for identifying patients at increased risk of CPAF in patients with ESUS.

Rivaroxaban concentrations in acute stroke patients with different dosage forms.

BACKGROUND: The crushed-tablet rivaroxaban concentration has been previously reported to be lower than the non-crushed concentration. However, the rivaroxaban concentration of fine granules has not yet been investigated. The anticoagulation intensity of rivaroxaban with fine granules, tablets, and crushed tablets was compared in acute stroke patients to assess the efficacy of each form. METHODS AND FINDINGS: Hospitalized patients over 75 years old with acute stroke who started taking rivaroxaban from April 2012 to September 2017 were included. Blood samples were drawn just before and 4 hours after taking rivaroxaban on a median of 5 days after treatment initiation for concentration measurements (C0h, C4h) based on an anti-factor Xa chromogenic assay. Of 114 patients (49 female, 83±5 years old), 97 had ischemic strokes, 9 had transient ischemic attacks, and 8 had intracerebral hemorrhages. Rivaroxaban was administered a median of 7 days after onset. Of these, 38 patients were given the 15 mg dose, and 76 were given the 10 mg dose. In the 15 mg dose group, C0h was significantly higher in the fine granule group than in the crushed tablet group, with no significant difference compared to the tablet group [C0h: 27.6±6.8 vs 4.0±4.1 (P = 0.01) vs. 33.3±25.2 ng/ml, (P = 0.51), respectively], as was C4h [223.0±66.6 vs 103.0±79.5 (P = 0.02) vs. 229.5±121.6 ng/ml (P = 0.88)]. In the 10 mg dose group, C0h was significantly higher in the fine granule group than in the crushed tablet group and comparable to that in the tablet group [23.2±7.9 vs 7.5±6.2 (P<0.01) vs 19.0±15.8 ng/ml, (P = 0.35)], as was C4h [150.7±85.4 vs 85.1±46.8 (P<0.01) vs 189.8±92.7 ng/ml (P = 0.18)]. CONCLUSIONS: The rivaroxaban concentration with fine granules was consistent with that in the tablet group and higher than that in the crushed tablet group.

Anti-Xa Activity and Event Risk in Patients With Direct Factor Xa Inhibitors Initiated Early After Stroke.

BACKGROUND: Measuring anti-Xa activity (AXA) has been reported as useful for predicting future risk of hemorrhagic and ischemic events in stroke patients taking direct factor Xa inhibitors. We evaluated AXA levels of rivaroxaban or apixaban in acute stroke patients with non-valvular atrial fibrillation. Methods and Results: This was a single-center, prospective, observational study. Consecutive patients with acute ischemic stroke or transient ischemic attack who were admitted within 7 days of onset and started taking rivaroxaban or apixaban for NVAF between January 2012 and April 2017 were enrolled. AXA was measured at 2 time points: just before (AXAtrough) and 4 h after (AXApeak) taking rivaroxaban or apixaban on the 2nd day or later of administration. Of 156 patients taking rivaroxaban, hemorrhagic events occurred in 13. Patients with hemorrhagic events had higher AXApeak than those without [median (interquartile range): 1.93 (1.11-3.75) vs. 1.35 (0.80-2.00) IU/mL; P<0.01]. Multivariable-adjusted Cox models showed that AXApeak was independently related to the incidence of hemorrhagic events. Of 169 patients taking apixaban, hemorrhagic events occurred in 11. Patients with hemorrhagic events had higher AXAtrough [2.78 (1.90-3.53) vs. 1.42 (0.93-2.08) IU/mL, P<0.01] and AXApeak [4.05 (3.44-4.72) vs. 2.43 (1.79-3.35) IU/mL, P<0.01] than those without. Both AXAtrough and AXApeak were independently related to the incidence of hemorrhagic events. CONCLUSIONS: In these patients who started rivaroxaban or apixaban early after stroke, AXA levels in the early period were related to future hemorrhagic events.

A case of cardioembolic stroke due to intracardiac papillary fibroelastoma evaluated by using transesophageal echocardiography.

A 62-year-old woman had a prior ischemic stroke in the right temporal lobe with dysarthria and dysesthesia of the left hand. Embolic stroke of undetermined source (ESUS) was diagnosed and warfarin was administered. However, transient ischemic attack recurred upon admission to our hospital. Paroxysmal atrial fibrillation and cerebral arterial stenotic lesions were absent. Transesophageal echocardiography revealed a mobile hyperechoic structure on the aortic valve indicating papillary fibroelastoma. She was diagnosed with a brain embolism due to the intracardiac tumor which was surgically excised and pathologically confirmed as papillary fibroelastoma. This type of tumor is relatively rare but it is important as an embolic source especially in ESUS. Transesophageal echocardiography was indispensable for detecting the embolic source in this patient with ESUS.

Tetraplatinum cluster complexes bearing hydrophilic anchors as precursors for γ-Al2O3-supported platinum nanoparticles.

Tetraplatinum cluster complexes bearing hydrophilic anchors, [Pt4(µ-OCOCH3)4(µ-OCOC6H4OH-4)4] (2a), [Pt4(µ-OCOCH3)4(µ-OCOC6H4B(OH)2-4)4] (2b), and [Pt4(µ-OCOCH3)4(µ-OCOC6H4NH2-4)4] (2c), were successfully prepared by a selective substitution reaction of four in-plane acetates of [Pt4(µ-OCOCH3)8] (1) with the corresponding p-substituted benzoic acids. Solid-state structure determination of 2a revealed the 3D network structure through intermolecular hydrogen bonding between the hydroxy group of the p-hydroxybenzoate ligand and the oxygen atom of the carboxylate ligand of 2a. UV-vis analysis of 2a­c in CH3CN or CH3CN­H2O in the presence of γ-Al2O3 clearly indicated the adsorption efficiency of these platinum clusters on γ-Al2O3: 2a bearing a hydroxyl group and 2b bearing a B(OH)2 group were effectively deposited onto γ-Al2O3 from CH3CN solution, whereas less than 40% of 1 and 2c were chemically adsorbed onto γ-Al2O3. Highly dispersed and very small platinum nanoparticles (less than 1 nm) on γ-Al2O3 were obtained by thermal treatment of Pt4-deposited γ-Al2O3 at 500 °C.