Sohei Yoshimura

Takotsubo Cardiomyopathy in Acute Ischemic Stroke

Takotsubo cardiomyopathy, which is characterized by transient left ventricular apical ballooning, is a known complication of subarachnoid hemorrhage. The aim of this study was to identify the clinical characteristics of acute ischemic stroke patients who experienced development of takotsubo cardiomyopathy.

ABCD3 and ABCD3-I Scores Are Superior to ABCD2 Score in the Prediction of Short- and Long-Term Risks of Stroke After Transient Ischemic Attack

Background and Purpose— Several risk scores have been developed to predict the stroke risk after transient ischemic attack (TIA). However, the validation of these scores in different cohorts is still limited. The objective of this study was to elucidate whether these scores were able to predict short-term and long-term risks of stroke in patients with TIA. Methods— From the Fukuoka Stroke Registry, 693 patients with TIA were followed up for 3 years. Multivariable-adjusted Cox proportional hazards model was used to assess the hazard ratio of risk factors for stroke. The discriminatory ability of each risk score for incident stroke was estimated by using C-statistics and continuous net reclassification improvement. Results— The multivariable-adjusted Cox proportional hazards model revealed that dual TIA and carotid stenosis were both significant predictors for stroke after TIA, whereas abnormal diffusion-weighted image was not. ABCD3 (C-statistics 0.61) and ABCD3-I (C-statistics 0.66) scores improved the short-term predictive ability for stroke (at 7 days) compared with the ABCD2 score (C-statistics 0.54). Addition of intracranial arterial stenosis (at 3 years, continuous net reclassification improvement 30.5%; P<0.01) and exclusion of abnormal diffusion-weighted imaging (at 3 years, continuous net reclassification improvement 24.0%; P<0.05) further improved the predictive ability for stroke risk until 3 years after TIA. Conclusions— The present study demonstrates that ABCD3 and ABCD3-I scores are superior to the ABCD2 score for the prediction of subsequent stroke in patients with TIA. Addition of neuroimaging in the ABCD3 score may enable prediction of long-term stroke risk after TIA.

Sex difference in the prevalence of deep-vein thrombosis in Japanese patients with acute intracerebral hemorrhage.

Background: Stroke patients often develop deep-vein thrombosis (DVT), a potential cause of pulmonary thromboembolism. Little information is available on DVT in Asian patients with intracerebral hemorrhage (ICH). Methods: We prospectively enrolled consecutive acute ICH patients. The main exclusion criteria were neurosurgical treatment, early death and coagulation disorders. DVT was evaluated using venous duplex ultrasonography on the day of admission, as well as 7 and 14 days later. Underlying characteristics, stroke features and laboratory data on admission were compared between patients who developed DVT by 14 days and those who did not. Results: A total of 81 (50 men, mean age 65 years, median NIH Stroke Scale, NIHSS, score 12) of 117 Japanese ICH patients were enrolled. DVT was detected in 4 patients on admission and was newly detected in 9 at 7 days. By 14 days, 17 patients (21%) were diagnosed as having DVT without thromboembolic complications, although 1 patient developed pulmonary thromboembolism. DVT was detected in the soleal veins of all 17 patients, followed by the peroneal veins (7 patients). After adjustment for age and related confounders, female sex was the only independent predictor for DVT (odds ratio 6.89, 95% confidence interval, CI, 1.56–36.34, p = 0.014). Female patients with an initial NIHSS score ≥12 had 19 times the risk for DVT compared to men with an NIHSS score <12 (95% CI 2.61–213.77, p = 0.007). Conclusions: DVT formation was not rare in Japanese ICH patients. Contrary to previous findings reported from western countries, female sex was strongly associated with DVT formation.

NAD(P)H oxidase p22phox C242T polymorphism and ischemic stroke in Japan: the Fukuoka Stroke Registry and the Hisayama study.

The C242T polymorphism of p22phox, a component of NAD(P)H oxidase, may have an impact on cardiovascular diseases; however, the association between this polymorphism and brain infarction is not fully understood. Here, we investigate the relationship between the C242T polymorphism and brain infarction in Japan. We recruited 1055 patients with brain infarction and 1055 control subjects. A chi‐squared test revealed that the T‐allele frequency was lower in patients with cardioembolic infarction (5.6%) than in control subjects (11.0%, P < 0.001); however, allele frequencies in patients with lacunar and atherothrombotic infarction (11.2%) were not significantly different from those in control subjects (11.0%). A multivariate‐adjusted conditional logistic regression analysis also revealed no association between CT + TT genotype, and lacunar and atherothrombotic infarction (odds ratio = 0.97, 95% confidence interval: 0.72–1.32). To investigate the functional effects of the C242T polymorphism, we examined superoxide production in COS‐7 cells cotransfected with Nox4 and p22phox of each genotype. The superoxide‐producing activity in those cells expressing p22phox with the T allele was not significantly different from that in cells expressing p22phox with the C allele. The present results suggest that the p22phox C242T polymorphism may have a protective effect against cardioembolic infarction, but is not related to lacunar and atherothrombotic infarction in Japan.

Three-month risk-benefit profile of anticoagulation after stroke with atrial fibrillation: The SAMURAI-Nonvalvular Atrial Fibrillation (NVAF) study

Aims This study was performed to determine the short-term risk-benefit profiles of patients treated with oral anticoagulation for acute ischemic stroke or transient ischemic attack using a multicenter, prospective registry. Methods A total of 1137 patients (645 men, 77 ± 10 years old) with acute ischemic stroke/transient ischemic attack taking warfarin (662 patients) or non-vitamin K antagonist oral anticoagulants (dabigatran in 205, rivaroxaban in 245, apixaban in 25 patients) for nonvalvular atrial fibrillation who completed a three-month follow-up survey were studied. Choice of anticoagulants was not randomized. Primary outcome measures were stroke/systemic embolism and major bleeding. Results Both warfarin and non-vitamin K antagonist oral anticoagulants were initiated within four days after stroke/transient ischemic attack onset in the majority of cases. Non-vitamin K antagonist oral anticoagulant users had lower ischemia- and bleeding-risk indices (CHADS2, CHA2DS2-VASc, HAS-BLED) and milder strokes than warfarin users. The three-month cumulative rate of stroke/systemic embolism was 3.06% (95% CI 1.96%–4.74%) in warfarin users and 2.84% (1.65%–4.83%) in non-vitamin K antagonist oral anticoagulant users (adjusted HR 0.96, 95% CI 0.44–2.04). The rate of major bleeding was 2.61% (1.60%–4.22%) and 1.11% (0.14%–1.08%), respectively (HR 0.63, 0.19–1.78); that for intracranial hemorrhage was marginally significantly lower in non-vitamin K antagonist oral anticoagulant users (HR 0.17, 0.01–1.15). Major bleeding did not occur in non-vitamin K antagonist oral anticoagulant users with a CHADS2 score <4 or those with a discharge modified Rankin Scale score ≤2. Conclusions Stroke or systemic embolism during the initial three-month anticoagulation period after stroke/transient ischemic attack was not frequent as compared to previous findings regardless of warfarin or non-vitamin K antagonist oral anticoagulants were used. Intracranial hemorrhage was relatively uncommon in non-vitamin K antagonist oral anticoagulant users, although treatment assignment was not randomized. Early initiation of non-vitamin K antagonist oral anticoagulants during the acute stage of stroke/transient ischemic attack in real-world clinical settings seems safe in bleeding-susceptible Japanese population.

Ulcerated plaques in the aortic arch contribute to symptomatic multiple brain infarction

Background The configuration of aortic plaque appears to be as important as its thickness when it acts as an embolic source to the brain. The frequency and clinical predictors of ulcerated plaque at the aortic arch identified using transoesophageal echocardiography (TOE) in patients with stroke were determined, and the association between the ulcer and recent ischaemic stroke, particularly multiple brain infarcts, which appear to indicate embolic stroke, was examined. Methods Aortic and cardiac embolic sources were evaluated using TOE in 360 patients with fresh ischaemic stroke proven by diffusion-weighted MRI, including 210 patients with a single infarct and 150 with multiple infarcts, as well as in 101 non-stroke control patients. An ulcer was defined as a crater on the plaque ≥2.0 mm in depth and width. Results An ulcerated plaque was identified in 10.6% of patients with stroke versus 2.0% of non-stroke patients, showing a 5.11-fold higher frequency in patients with stroke (95% CI 1.51 to 31.96) after adjustment for age and sex. After multivariate adjustment for clinical and ultrasonographic features, multiple-infarct patients had a 7.61-fold higher risk (95% CI 1.99 to 50.43) of having an ulcer than control patients and a 3.32-fold higher risk (95% CI 1.61 to 7.18) of having an ulcer than single-infarct patients. Diabetes mellitus and drinking habit were independently related to the presence of ulcerated plaque in patients with stroke. Conclusions Ulcerated plaque in the aortic arch was associated with the development of ischaemic stroke, especially multiple brain infarcts, probably involving, at least in part, an embolic mechanism.

Cerebral sinus thrombosis in a patient with Cushing’s syndrome

It is well known that hypercortisolism induced by Cushing’s disease and syndrome, or by administration of glucocorticoids, causes thromboembolic complications.1 However, the precise mechanisms underlying the hypercortisolism induced hypercoagulable state still remain unknown. Here we describe a case of cerebral lateral sinus thrombosis with Cushing’s syndrome. Glucocorticoid induced overproduction of factor VIII and von Willebrand factor (VWF) may have contributed to the development of the cerebral sinus thrombosis in this patient. A mildly obese 30 year old woman was admitted to our hospital because of headache and nausea. She was not taking any medications, including oral contraceptives, before admission. The patient had no intracranial hypertension; her fundi showed no papillo-oedema, and intracranial pressure measured by lumbar puncture was normal (14.3 mmHg). Brain computed tomogram (CT) showed a high density lesion in the left temporo-occipital lobe (fig 1A). Magnetic resonance venogram (MRV) on the first hospitalised day showed a filling defect in the left lateral sinus (fig 1B). These findings were consistent with cerebral lateral sinus thrombosis. Figure 1  (A) Brain CT shows …

Cerebral Atherosclerosis in Japanese. I. Age Related to Atherosclerosis

During a period of approximately two years (1965 through 1966), 717 intracranial cerebral arteries (males and females) were obtained from the medicolegal autopsy cases. Systematic grading of the macroscopic severity of cerebral atherosclerosis was performed and the results were reported. In general, cerebral atherosclerosis appeared as early as the second decade and increased in severity with age, particularly at the fifth decade in males and the sixth decade in females. The prevalence of localization of early and/or severe cerebral atherosclerosis was studied. The results in the present study were not the same as in the previous investigations on Caucasians. The common sites of the severe cerebral atherosclerosis causing marked lumen narrowing were the proximal portion of posterior cerebral arteries, peripheral portion of the middle cerebral arteries, and the vertebral arteries and their fusing site at the basilar artery; the internal carotid artery was the least commonly involved. In the present study, the influence of sex in the production of cerebral atherosclerosis was suggested, and the simple senescence theory of cerebral atherosclerosis was not supported. The macroscopic severity of cerebral atherosclerosis of Japanese in the present study appeared to be equal to or slightly greater than that in Americans and Norwegians reported by Baker et al.

Polymorphisms in the Lymphotoxin Alpha Gene and the Risk of Ischemic Stroke in the Japanese Population

Background and Purpose: Lymphotoxin α (LTA), one of the tumor necrosis factor family proteins, is an important proinflammatory cytokine and appears to play a putative role in the inflammatory process of atherosclerosis. Recent genetic studies have suggested that variations in the gene encoding LTA, which affect its expression and biological function, may contribute to the development of vascular diseases. We conducted a case-control study to clarify the association of LTA gene polymorphisms with ischemic stroke in a large Japanese population. Methods: Genotyping for LTA A252G and C804A polymorphisms was achieved by a rapid-cycle polymerase chain reaction and melting curve analysis using fluorescent probes in 1,044 incident cases of ischemic stroke recruited from the Fukuoka Stroke Registry and 1,044 age- and sex-matched control subjects recruited from the Hisayama Study. Results: The overall distribution of allele and genotype for each polymorphism was similar between stroke patients and control subjects. The allele frequencies of 252G and 804A were slightly lower in stroke patients than in control subjects; however, conditional logistic regression analysis adjusted for potential risk factors found no association between the risk of ischemic stroke and either polymorphism. In terms of stroke subtype, we also found no association of these polymorphisms with any subtypes of ischemic stroke. Conclusions: Neither the A252G nor C804A polymorphism of the LTA gene was associated with stroke overall and any subtypes of ischemic stroke in the Japanese population.

Polymorphism in the sorbin and SH3-domain-containing-1 (SORBS1) gene and the risk of brain infarction in the Japanese population: the Fukuoka Stroke Registry and the Hisayama study

Background and purpose:  Sorbin and SH3‐domain‐containing‐1 (SORBS1) is an important adaptor protein in insulin‐signalling pathway, and its genetic polymorphism may regulate the activity of insulin resistance. We investigated the association between the SORBS1 T228A polymorphism and ischaemic stroke.