Intracardiac Thrombus Following Rivaroxaban Treatment in a Patient with Atrial Fibrillation Associated with Rheumatic Heart Disease.

We report a case of atrial fibrillation with rheumatic heart disease (RHD) who had intracardiac thrombus and cardiogenic cerebral embolism with rivaroxaban therapy. Intracardiac thrombus disappeared after switching from rivaroxaban to warfarin. Patients of RHD have the possibility of gradual progression of valvular disease even if they are old, so we need to distinguish nonvalvular atrial fibrillation from RHD before starting direct oral anticoagulants.

A case of recanalization of innominate artery and right middle cerebral artery embolism due to cardiogenic cerebral infarction with anticoagulation therapy.

An 80-year-old woman had an aortic valve replacement 1 month before admission and took warfarin for transient atrial fibrillation. She developed a disturbance of consciousness and left hemiplegia. On admission, the right radial artery was slightly palpable. Head MRI images showed a hyper-intense area in the right middle cerebral artery territory. MRA images showed an occlusion of the right M1 distal site and decreased signal at the right internal carotid artery. Contrast CT images of the ascending aorta showed an embolus in the innominate artery. She was diagnosed with an innominate artery saddle embolus and occlusion of the right cerebral artery due to cardiac embolism. She was treated with a heparin infusion and warfarin. She recovered consciousness and from hemiplegia gradually. Recanalization of the innominate artery and right cerebral artery was confirmed. In cases where the radial artery is slightly palpable, it is necessary to consider an innominate artery saddle embolus in addition to aortic dissection.

Internal carotid artery dissection caused by an elongated styloid process: usefulness of transoral ultrasonography.

We report a case of internal carotid artery (ICA) occlusion caused by arterial dissection triggered by an elongated styloid process. A 43-year-old man presented with a headache followed by speech disturbance. Magnetic resonance imaging and magnetic resonance angiography scans revealed acute infarction and right ICA occlusion. A T1-weighted magnetic resonance imaging scan revealed a hyperintensity in the occluded ICA, suggesting intramural hematoma. Computed tomographic angiography also revealed ICA occlusion and bilateral elongated styloid processes. We performed transoral carotid ultrasonography, which revealed the absence of flow signal in the double lumen of the dilated extracranial ICA. We diagnosed his condition as arterial dissection and treated him with antithrombotic drugs. Six months later, the occluded ICA recanalized spontaneously, and computed tomographic angiography at that time revealed a close relation between the tip of the styloid process and the recanalized ICA. This finding suggests that an elongated styloid process is involved in arterial dissection. In patients with ICA occlusion of unknown etiology, an evaluation for intramural hematoma and styloid process length are useful for the diagnosis of dissection and its etiology.

High plasma D-dimer is a marker of deep vein thrombosis in acute stroke.

This study investigated whether plasma D-dimer level is useful for detection of deep vein thrombosis (DVT) in patients with acute stroke. A total of 133 patients hospitalized within 3 days after stroke onset underwent duplex venous ultrasonographic examination of the lower limbs and repeated measurements of plasma D-dimer level. DVT was detected in 36 of 100 patients with ischemic stroke and in 25 of 33 patients with intracerebral hemorrhage (ICH) (76%; P < .001). Plasma D-dimer level on admission (7.5 ± 10.7 µg/mL vs 3.7 ± 10.1 µg/mL; P = .040) and its maximum level before the ultrasonographic examination (29.1 ± 48.7 µg/mL vs 5.5 ± 11.0 µg/mL; P < .001) were higher in the patients with DVT compared with those without DVT. On multivariate logistic regression analysis, the maximum D-dimer level was independently related to the identification of DVT (odds ratio [OR] 1.05; 95% confidence interval [CI], 1.00-1.09 per 1-µg/mL increase; P = .045), but the admission D-dimer level was not when it was included instead of the maximum D-dimer level. In addition, female sex (OR, 4.99), ICH (OR, 5.20), high Wells clinical score (OR, 2.40 per 1-point increase), and low protein level (OR, 0.21 per 1-g/dL increase) were independently related to the identification of DVT. The optimum cutoff value of the maximum D-dimer level for positive DVT was 5.5 µg/mL (sensitivity, 89%; specificity, 82%). Our findings suggest that high plasma D-dimer level during the course of acute stroke can help detect DVT on duplex venous ultrasonography.

Cerebral microbleeds predict impending intracranial hemorrhage in infective endocarditis.

BACKGROUND: Cerebral microbleeds (CMBs) detected by T2*-weighted MRI are a potential indicator of hypertension, microvascular disease and hemorrhagic stroke. An association between infective endocarditis (IE) and CMBs has been reported recently, but the clinical significance remains unclear. We hypothesized that CMBs in patients with IE are associated with vascular vulnerabilities such as mycotic aneurysm or pyogenic vasculitis. METHODS: We retrospectively reviewed 26 consecutive patients with definite IE who underwent T2*-weighted MRI and were admitted to 2 medical centers in Osaka, Japan, between January 2006 and June 2010. We examined the incidence of symptomatic intracranial hemorrhage (ICH) occurring after initial MRI examination and investigated the association between ICH, CMBs and other clinical characteristics. RESULTS: CMBs were identified in 14 patients (54%), and 72% of CMBs were found in the lobar region. Symptomatic ICH was observed in 8 patients (31%) during the 3-month follow-up period after initial MRI examination. In multiple logistic regression analyses, the presence of preceding ICH [odds ratio (OR) 40.0, 95% confidence interval (CI) 2.5-2,870] and the presence of CMBs (OR 34.0, 95% CI 1.3-17,300) were independent predictors of the development of ICH. Using cutoff values for CMBs of ≥2 and ≥3, the adjusted ORs for ICH increased (OR 42.1, 95% CI 1.9-24,300, and OR 70.1, 95% CI 2.5-105,000, respectively). CONCLUSIONS: In addition to prior ICH, the presence of CMBs was a strong predictor of impending ICH in patients with IE. CMBs might represent vascular vulnerability related to IE.

Preadmission therapeutic anticoagulation reduces cerebral infarct volume in patients with nonvalvular atrial fibrillation.

AIM: We investigated the influence of preadmission anticoagulation on infarct volume in patients with nonvalvular atrial fibrillation (NVAF). METHODS: Data were collected on consecutive ischemic stroke patients with NVAF admitted to Osaka University Hospital between 2004 and 2011. Patients were divided into 3 groups: the no-anticoagulation group, the subtherapeutic anticoagulation group [admission prothrombin time international normalized ratio (PT-INR) <1.6], and the therapeutic anticoagulation group (PT-INR ≥1.6). In analyses of neurological outcome, we excluded patients with a modified Rankin Scale (mRS) score of >1 before onset. RESULTS: Of the 68 patients, 45 were classified into the no-anticoagulation group, 9 into the subtherapeutic group, and 14 into the therapeutic group. The median value of infarct volume was 60 (interquartile range 9-176), 142 (64-184), and 8 (3-46) ml in each group, respectively. Infarct volume in the therapeutic group was significantly smaller than in the subtherapeutic group (p = 0.010), and tended to be smaller than in the no-anticoagulation group (p = 0.086). National Institute of Health Stroke Scale score at admission, and mRS score at discharge were significantly reduced in the therapeutic group compared with those in the other groups (p = 0.028 and p = 0.017, respectively). CONCLUSION: Therapeutic anticoagulation reduces infarct volume and improves neurological outcome after ischemic stroke in patients with NVAF.

Clinical significance of oral intake in patients with acute stroke.

We investigated the feeding method and predictors for oral intake difficulty for a month after acute stroke. In 107 consecutive patients, swallowing function was assessed using a bedside screening protocol within 48 h of admission. The method of feeding was followed for 4 weeks, and predictors for "non-oral intake" on admission and 4 weeks later were analyzed. Sixty-two patients (58%) were fed any type of food orally within 48 h of admission, and 91 patients (84%) were fed orally 4 weeks later. Independent predictors for non-oral intake within 48 h of admission were consciousness disturbance (not completely alert; OR = 12.3), absence of gag reflex (OR = 5.34), and NIHSS score (OR = 1.20 per one point). Independent predictors for non-oral intake after 4 weeks were absence of gag reflex (OR = 7.95) and NIHSS score (OR = 1.13 per one point) on admission. Only four (9%) patients in the non-oral intake group within 48 h of admission and no patients in the non-oral intake group 4 weeks after admission were discharged to home. In acute stroke patients, absence of the gag reflex and severe neurologic deficits on admission predict prolonged dysphagia lasting longer than a month. Patients who could not eat orally had poor outcome.

Quantitative evaluation of carotid plaque echogenicity by integrated backscatter analysis: correlation with symptomatic history and histologic findings.

BACKGROUND AND PURPOSE: Echogenicity of carotid plaque well reflects the risk of ischemic stroke and may be predictive of the histologic content of the plaque. However, objective evaluation of plaque echogenicity has been hampered by a lack of established quantitative measures. This study examined the relation between echogenicity assessed by integrated backscatter (IBS) analysis and (1) symptomatic history and (2) histologic features of carotid plaques. METHODS: We used acoustic densitometry to quantify by IBS analysis the echogenicity of 31 carotid plaques of 26 patients undergoing carotid endarterectomy or stenting. IBS was subsequently compared with histologic findings of the respective tissue in 10 patients who underwent endarterectomy. The IBS value was calibrated with 2 reference structures (vessel lumen and adventitia) as the IBS index. RESULTS: The IBS index of symptomatic plaques was lower than that of asymptomatic plaques (23.1 +/- 12.5 vs. 36.5 +/- 18.2, p < 0.05). The IBS index in fatty/necrotic atheromatous sites (n = 20, 16.6 +/- 10.7) was lower than that in fibrous (n = 26, 42.4 +/- 13.6, p < 0.01) or calcified (n = 11, 87.7 +/- 17.4, p < 0.01) sites and the same as that in intraplaque hemorrhagic sites (n = 50, 23.6 +/- 16.9). CONCLUSIONS: Carotid plaque echogenicity, as quantitatively assessed by IBS analysis, correlates well with the presence or absence of prior symptoms and histologic contents of the plaques. IBS analysis may aid in the assessment of carotid plaque-related risk of stroke.

Relationship between detectability of ischemic lesions by diffusion-weighted imaging and embolic sources in transient ischemic attacks.

BACKGROUND/AIMS: The aim of this study is to clarify the relationship between lesion detectability by diffusion-weighted magnetic resonance imaging (DWI) and the etiology of transient ischemic attacks (TIAs). METHODS: A retrospective study was performed on 72 patients with carotid TIAs who underwent DWI studies within 2 weeks after the last episode. RESULTS: Lesions were detected in 24 of 72 patients (33%). The detectability of lesions was 12% (3/25) in the large-artery atherosclerosis (LA) group, 57% (8/14) in the cardioembolism (CE) group, 8% (1/13) in the small-artery occlusion (SA) group, and 60% (12/20) in the other etiology or undetermined etiology (UD) group. Detectabilities in the CE group and the UD group were higher than those in the LA and SA groups. Of 24 patients with DWI-positive lesions, 17 (71%) had embolic sources in the heart; 9 were classified in the UD group because they had embolic sources both in the heart and large artery. CONCLUSION: Ischemic DWI lesions in TIAs are most likely caused by a cardioembolic mechanism. In TIA patients showing lesions on DWI, heart disease should be surveyed as the possible embolic source.

Moderate atheroma of the aortic arch and the risk of stroke.

BACKGROUND AND PURPOSE: Severe atheroma >or=4 or 5 mm of the aortic arch is a risk factor for stroke. We investigated the most predictive characteristics of arch atheroma, including maximal plaque thickness, for subsequent cardiovascular events, and also examined whether moderate atheroma<4 mm is a risk of cerebral emboli. METHODS: The maximal plaque thickness (MPT) and plaque morphologies of the aortic arch were evaluated by transesophageal echocardiography in 236 patients with ischemic stroke. We assessed the relationship between the incidence of cardiovascular events, recurrent stroke or myocardial infarction, and the characteristics of the atheroma. We also investigated the thickness of atheroma in patients with known causes of stroke (n=148) and in patients with undetermined causes (n=19). RESULTS: Cardiovascular events occurred in 47 patients in the follow-up period with a mean of 3.5 years. MPT was a significant risk factor of the cardiovascular events, although plaque morphologies were not. For the receiver operator characteristics curve analysis, the suitable cutoff point of MPT associated with the cardiovascular events was 3.5 mm. Patients with MPT >or=3.5 mm had a higher risk of cardiovascular events than did those with MPT<3.5 mm. In addition, aortic atheroma with MPT >or=3.5 mm was more frequently observed in patients with undetermined causes of stroke than those with known causes at 68 vs. 39% (p=0.024). CONCLUSIONS: MPT >or=3.5 mm is the best predictor of subsequent cardiovascular events and a possible cause of embolic stroke.

Right-to-left shunt evaluated at the aortic arch by contrast-enhanced transesophageal echocardiography.

OBJECTIVE: The right-to-left shunt (RLS) is diagnosed by contrast-enhanced transesophageal echocardiographic monitoring of the bilateral atria (cTEE-BA). However, the procedure is often disturbed by nonsmoke spontaneous individual contrast (NSSIC) with fast motion, which appears in the left atrium after respiratory maneuvers without administration of a contrast medium and moves past in several seconds. We attempted to perform cTEE monitoring of the aortic arch (cTEE-AA) for evaluation of the RLS and compared the findings with those of cTEE-BA. METHODS: Both cTEE-BA and cTEE-AA were performed in 168 patients with ischemic stroke (133 men and 35 women; mean age +/- SD, 62.0 +/- 14.4 years). The frequency of NSSIC in the left atrium was compared with that in the aortic arch during the respiratory maneuver. When contrast much brighter than the NSSIC was visualized in the left atrium and the aortic arch during the respiratory maneuver with administration of the contrast medium, we considered the RLS to be positive in the cTEE-BA and cTEE-AA, respectively. Findings were then compared between the 2 examinations. RESULTS: Nonsmoke spontaneous individual contrast was more frequently observed in the left atrium than the aortic arch (61.3% versus 14.9%; chi2 test, P < .0001). The RLS was positive in 34 patients in the cTEE-BA and in 39 patients in the cTEE-AA. The sensitivity and specificity of the cTEE-AA for the cTEE-BA were 100% and 96.3%, respectively. CONCLUSIONS: The cTEE-AA may be an alternative method for detection of an RLS, especially in patients with a large amount of NSSIC in the left atrium.

Estimation of circulating blood volume in infants using the pulse dye densitometry method.

BACKGROUND: Estimation of hemodynamics is important for critically ill infants. Pulse dye densitometry (PDD) using indocyanine green (ICG), which enables measurements of circulating blood volume at the bedside, has recently been developed for adults. METHODS: We conducted a basic investigation to determine whether this method can be applied to infants and measured circulating blood volume in 25 infants whose gestational ages ranged from 24 to 40 weeks (median, 32 weeks). At first, to validate the accuracy of measurements, arterial ICG concentrations determined by blood sample measurements were compared using a spectrophotometer ([ICG blood]) and by noninvasive measurement using PDD ([ICG pdd]) in seven infants. Next, blood volumes in 25 infants were estimated by the PDD method. RESULTS: There was a positive relationships between [ICG blood] and [ICG pdd] (r = 0.913, P < 0.0001). Using Bland Altman analysis, the bias between the two methods was 0.24 +/- 0.30 mg.l(-1) (95% confidence interval: 0.39-0.09 mg.l(-1)) and the limits of agreement (2 sd) were -0.36 and 0.84 mg.l(-1), respectively. Mean (sd) blood volume was 94.9 ml.kg(-1) (24.3). The values obtained by this study are almost the same as previously reported values obtained by using other methods. CONCLUSIONS: PDD using ICG can be used to monitor of hemodynamics in infants.

[Stroke recurrence in patients with brain embolism and patent foramen ovale--association with deep vein thrombosis detected by ultrasonography].

Paradoxical embolism through a patent foramen ovale (PFO) is a recognized cause of stroke, but its prognosis is not well known. The aim of our study is to evaluate differences in risk factors, recurrent stroke subtypes and effects of various preventive therapies between PFO associated stroke patients with and without deep vein thrombosis (DVT). A total of 63 patients who had an embolic stroke with a PFO within 3 months from stroke onset were enrolled. Venous ultrasonography, which was performed in all the patients, revealed DVT in 26 patients (41%). Venous thrombosis was confined to the isolated calf veins in 24 of 26 cases (92%). For prevention of stroke recurrence, warfarin was administrated in 32 patients, antiplatelet therapy was given in 21 patients, and combination of warfarin and antiplatelet therapy was chosen in 10 patients. Three patients with DVT and three other patients without DVT had recurrent ischemic events during a mean follow-up period of 14.6 months. In all the 3 patients without DVT, complicated aortic arch lesions were also observed, and 2 of them had lacunar infarcts. In all the three patients with DVT recurrent embolic stroke or TIA occurred in spite of anticoagulant therapy. Their INR values at the time of recurrence were all below 1.7, and 2 of them were associated with atrial septal aneurysm (ASA). Association with PFO, ASA, and DVT may be a substantial risk factor for recurrent stroke. Higher INR value in anticoagulation may be recommended for such patients to prevent stroke recurrence.

Noninvasive optical imaging in the visual cortex in young infants.

During the developmental stage, the brain undergoes anatomic, functional, and metabolic changes necessary to support the complex adaptive behavior of a mature individual. Estimation of developmental changes occurring in different regions of the brain would provide a means of relating various behavioral phenomena to maturation-specific brain structures, thereby providing useful information on structure-function relationships in both normal and disease states. We used multichannel near-infrared spectroscopy (MNIRS), a new noninvasive imaging technique for revealing the course of neural activity in selected brain regions, to monitor the activities of the visual cortex as mirrored by hemodynamic responses in infants subjected to photostimulation during natural sleep. In the infants, oxyhemoglobin and total hemoglobin decreased and deoxyhemoglobin increased in the visual cortex with photostimulation. This pattern of responses was different from the response pattern in adults reported previously. The different patterns of responses to photostimulation in the visual cortices of infants and adults might reflect developmental and behavioral differences. It may reflect a different functional organization of the visual cortex in infants or ongoing retinal development. Our results demonstrated that regional hemodynamic change could be detected in a small area around the visual cortex. MNIRS offers considerable potential for research and noninvasive clinical applications.

Vertebral artery occlusion in duplex color-coded ultrasonography.

BACKGROUND AND PURPOSE: To establish the diagnostic criteria for the site of occlusion in the vertebral arteries (VAs) using duplex color-coded ultrasonography. METHODS: In 128 consecutive patients who underwent conventional cerebral angiography, we prospectively measured the diameter, mean flow velocity (MV), peak systolic flow velocity, and end-diastolic flow velocity of both VAs. The diameter-ratio (diameter of contralateral VA divided by that of target VA) and MV-ratio (MV of contralateral VA divided by that of target VA) were determined. Based on the angiographic findings, we classified the VAs into 4 types (5 groups) as follows: (1) the origin of VA occlusion (Origin group: n=9); (2) VA occlusion before branching into the posterior inferior cerebellar artery (PICA) (Before group: n=10); (3A) symptomatic VA occlusion after branching into the PICA (After group: n=12); (3B) asymptomatic or hypoplastic occlusive VA after branching into the PICA (PICA end group: n=15); and (4) no significant occlusive lesions in the VA (Control group: n=194). RESULTS: No flow signals in the VAs apparently indicated the Origin group. Preserved peak systolic flow velocity but end-diastolic flow velocity of zero cm/s indicated the Before group. MV <18 cm/s and MV-ratio > or =1.4 indicated the PICA end group or After group. Furthermore, these groups could be distinguished as follows: a diameter-ratio <1.4 indicated the After group. A diameter-ratio > or =1.4 indicated the PICA end group. Either MV > or =18 cm/s or MV <18 cm/s in combination with MV-ratio <1.4 indicated the Control group. CONCLUSIONS: Duplex color-coded ultrasonography can accurately diagnose the site of VA occlusion.

Change of bilirubin photoisomers in the urine and serum before and after phototherapy compared with light source.

BACKGROUND: The clinical effect of phototherapy for neonatal hyperbilirubinemia is based on the production and elimination of cyclobilirubin. Generally, the clinical effect of light sources is estimated by the reduction in the total serum bilirubin level. One procedure with less invasiveness than blood collecting is urine collection. Whether the effectiveness of light sources used for phototherapy could be assessed using measurements of bilirubin photoisomers in urine was studied. METHODS: This study was a retrospective analysis of 38 term infants with hyperbilirubinemia who underwent phototherapy. Bilirubin fractions in serum and urine before and 24 h after the phototherapy were measured by high-performance liquid chromatography. The light sources used for the phototherapy were blue-white light (n = 11), Biliblanket plus high output (n = 13) or green light (n = 14). The relationships between serum and urine bilirubin photoisomers after phototherapy and whether the levels of urine bilirubin photoisomer are affected by the light sources with different wavelength characteristic were analyzed. RESULTS: There was no correlation between serum (ZE)-bilirubin and urine configurational isomers, but a weak positive correlation between serum (EZ)-cyclobilirubin and urine structural isomers after phototherapy. Although serum (ZE)-bilirubin levels depended on the wavelength characteristic of each light source during phototherapy, the urine configurational isomer levels did not depend on it. The increase in serum (EZ)-cyclobilirubin levels and the urine structural isomer levels were mostly in agreement. CONCLUSIONS: The urine bilirubin structural isomers may be used to estimate the serum (EZ)-cyclobilirubin levels and to evaluate the clinical effects of light sources.

Quantification of cerebral oxygenation by full-spectrum near-infrared spectroscopy using a two-point method.

The aim of this study was to quantify the relative concentrations of oxyhemoglobin and deoxyhemoglobin within the light path of the brain and to estimate cerebral hemoglobin (Hb) oxygen saturation using full-spectrum near-infrared spectroscopy (fsNIRS). For this purpose, we developed a novel exponential correction equation as well as a two-point spectroscopy method to estimate the relative concentrations of Hb and Hb oxygen saturation in biological tissues. The results of evaluation of measurements using an in vitro model indicated that our fsNIRS method enables accurate and non-invasive measurements of Hb content and saturation in a highly scattered medium such as the human brain. According to the results of analysis using a hypoxic piglet model, the mean cerebral Hb oxygen saturation (SbO(2)) of newborn piglets at an inspired oxygen gas concentration of 0.21 was estimated to be 63+/-4% (mean+/-S.D.). Umbilical arterial and left internal jugular venous Hb oxygen saturation were simultaneously estimated to be 96+/-2% and 52+/-11%, respectively. SbO(2) and arterial Hb oxygen saturation values had a linear relationship. The average oxygenation state of cerebral tissue is comparable with that of the cerebral vein. The results of this study showed that our method can be used to monitor Hb oxygen saturation in the neonatal brain at the bedside in an intensive care unit.

Measurement of cerebral oxygenation in neonates after vaginal delivery and cesarean section using full-spectrum near infrared spectroscopy.

To investigate whether or not the mode of delivery produces differences in cerebral oxygenation, cerebral hemoglobin oxygen saturation was measured using full-spectrum near infrared spectroscopy in 26 healthy term newborn infants immediately after birth. Infants in group 1 (n=20) were delivered vaginally, and those in group 2 (n=6) by elective cesarean section. Arterial oxygen saturation in the right hand was also measured simultaneously using a pulse oximeter. Changes in arterial oxygen saturation showed no significant difference between the two groups. The mean+/-S.D. of cerebral hemoglobin oxygen saturation in group 1 increased rapidly after birth, from 29+/-17% at 2 min to 68+/-6% at 8.5 min, followed by an almost constant value (66+/-7% at 15 min). In comparison, cerebral hemoglobin oxygen saturation in group 2 also increased rapidly until 8.5 min, but after this time decreased significantly to 57+/-5% at 15 min after birth. This indicates that the mode of delivery has a marked influence on cerebral oxygenation immediately after birth.