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Aim As altered blood flow in the cerebral perforating arteries (PA) might be related to development of cerebral white matter hyperintensities, we examined whether the hemodynamic relationship of the PA and middle cerebral artery (MCA) is altered in rat models of diabetes, compared with normal rats and a rat model of sinoatrial denervation (blood pressure fluctuation model). Methods We used microangiography with monochromatic synchrotron radiation to measure the diameters of the PA and MCA at 4.5 μm resolution in five groups of rats: (i) Long-Evans Tokushima Otsuka (LETO); (ii) Otsuka Long-Evans Tokushima Fatty (a model of type 2 diabetes with obesity); (iii) LETO with sinoaortic denervation (LETO + SAD); (iv) F344; and (v) F344 + streptozotocin (a model of type 1 diabetes). Results Compared with LETO, Otsuka Long-Evans Tokushima Fatty rats showed a significant reduction in the diameter of both PA and MCA, though the PA/MCA diameter ratio was unchanged. In contrast, compared with LETO, LETO + SAD rats showed an increased MCA diameter, and the PA/MCA diameter ratio was decreased. Compared with F344 rats, the MCA diameter was increased in F344 + streptozotocin rats, and the PA/MCA diameter ratio was decreased. Scatter diagrams showed that the diameters of the PA and MCA were essentially independent of each other in the two types of diabetic models. Conclusion PA were consistently visualized at high resolution by means of microangiography using synchrotron radiation. The present results show that rat diabetic models exhibit changes in PA diameter and PA/MCA diameter ratio, which might be related to the development of diabetes-associated cerebral white matter hyperintensities. Geriatr Gerontol Int 2015; 15 (Suppl. 1): 74–80.

The imaging and spectral performance of CdTe double-sided strip detectors (CdTe-DSDs) was evaluated for the ASTRO-H mission. The charcterized CdTe-DSDs have a strip pitch of 0.25 mm, an imaging area of 3.2 cm$\times$3.2 cm and a thickness of 0.75 mm. The detector was successfully operated at a temperature of $-20^\circ$C and with an applied bias voltage of 250 V. By using two-strip events as well as one-strip events for the event reconstruction, a good energy resolution of 2.0 keV at 59.5 keV and a sub-strip spatial resolution was achieved. The hard X-ray and gamma-ray response of CdTe-DSDs is complex due to the properties of CdTe and the small pixel effect. Therefore, one of the issues to investigate is the response of the CdTe-DSD. In order to investigate the spatial dependence of the detector response, we performed fine beam scan experiments at SPring-8, a synchrotron radiation facility. From these experiments, the depth structure of the electric field was determined as well as properties of carriers in the detector and successfully reproduced the experimental data with simulated spectra., Comment: 11 pages, 11 figures, published in proceedings for SPIE Astronomical Telescopes + Instrumentation in 2012

著者人数: 49名, Accepted: 2017-12-18, 資料番号: SA1170329000

A 54-year-old woman with adenocarcinoma of the lung and lymph node metastasis experienced nystagmus and cerebellar ataxia 2 weeks after initiating nivolumab therapy. An evaluation for several autoimmune-related antibodies and paraneoplastic syndrome yielded negative results. We eventually diagnosed the patient with nivolumab-induced acute cerebellar ataxia, after excluding other potential conditions. Her ataxic gait and nystagmus resolved shortly after intravenous steroid pulse therapy followed by the administration of decreasing doses of oral steroids. Nivolumab, an immune checkpoint inhibitor, is known to induce various neurological adverse events. However, this is the first report of acute cerebellar ataxia associated with nivolumab treatment.

Background and Purpose- We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome. Methods- We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2-4, ≥5, and10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3- to 6-month functional outcome (modified Rankin score2). Results- In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720 (3.3%) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95% confidence interval: 1.09-2.07; P=0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73-5.35; P0.001) but not symptomatic ICH. Both cerebral amyloid angiopathy and noncerebral amyloid angiopathy patterns of CMBs were associated with PH and PHr. Increasing CMB burden category was associated with the risk of symptomatic ICH ( P=0.014), PH ( P=0.013), and PHr ( P0.00001). Five or more and10 CMBs independently predicted poor 3- to 6-month outcome (odds ratio: 1.85; 95% confidence interval: 1.10-3.12; P=0.020; and odds ratio: 3.99; 95% confidence interval: 1.55-10.22; P=0.004, respectively). Conclusions- Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor 3- to 6-month functional outcome after intravenous thrombolysis for acute ischemic stroke.

A 63-year-old man presented with the loss of the sensations of pain and temperature sensation in the right facial region innervated by the trigeminal nerve (V1 to 3). He showed abnormal lesions in the pons and the trigeminal nerve on magnetic resonance imaging (MRI). He had recurrent herpes in the nasal cavity, and a history of left facial palsy. We herein present the unique MRI findings and suggest that herpes simplex infection may cause trigeminal neuropathy. This is the first reported case of dissociated trigeminal neuropathy with herpes simplex infection which was accompanied by a pontine lesion on MRI.

Hypoxia-inducible factor 1 (HIF-1) is regulated by the oxygen-dependent hydroxylation of proline residues by prolyl hydroxylases (PHDs). We recently developed a novel PHD inhibitor, TM6008, that suppresses the activity of PHDs, inducing continuous HIF-1α activation. In this study, we investigated how TM6008 affects cell survival after hypoxic conditions capable of inducing HIF-1α expression and how TM6008 regulates PHDs and genes downstream of HIF-1α. After SHSY-5Y cells had been subjected to hypoxia, TM6008 was added to the cell culture medium under normoxic conditions. Apoptotic cell death was significantly augmented just after the hypoxic conditions, compared with cell death under normoxic conditions. Notably, when TM6008 was added to the media after the cells had been subjected to hypoxia, the expression level of HIF-1α increased and the number of cell deaths decreased, compared with the results for cells cultured in media without TM6008 after hypoxia, during the 7-day incubation period under normoxic conditions. Moreover, the protein expression levels of heme oxygenase 1, erythropoietin, and glucose transporter-3, which were genes downstream of HIF-1α, were elevated in media to which TM6008 had been added, compared with media without TM6008, during the 7-day incubation period under normoxic conditions. However, the protein expression levels of PHD2 and p53 which suppressed cell proliferation were suppressed in the media to which TM6008 had been added. Thus, TM6008, which suppresses the protein expressions of PHD2 and p53, might play an important role in cell survival after hypoxic conditions, with possible applications as a new compound for treatment after ischemic stroke.

Background: Stroke guidelines recommend that thrombolytic therapy should be carried out within 60 minutes from the arrival at the hospital. CT may decrease door-to-treatment interval compared to MRI. However, MRI may provide more information on brain pathology to select the treatment than CT. Thus, it remains controversial which is informative for selecting thrombolysis and endovascular treatment in acute ischemic stroke between CT and MRI. Purpose: Purpose of this study is to evaluate which clinical risk score using CT or MRI presents the best predictive performance for symptomatic intracranial hemorrhage (SICH). Methods: Consecutive stroke patients suffering anterior circulation were analyzed, who were received IV rt-PA therapy between October 2005 and March 2016. We calculated nine scores for each patient: DRAGON, MRI-DRAGON, HAT, SEDAN, SITS-ICH, SPAN-100, ASTRAL, PRS, and GRASPS. The area under the receiver operating characteristic curve was calculated to determine the predictive performance of each SICH predictive score according to two criteria: NINDS and ECASS-II. Logistic regression determined the odds ratio for two SICH criteria. Results: A total of 166 acute ischemic stroke patients were analyzed (113 men, 72±12 years old). SICH defined following NINDS criteria occurred in 14 patients, SICH defined following ECASS criteria occurred in 11 patients. 144 patients were performed both CT and MRI [median time between CT and MRI, 11; IQR 8-16]. Only 2 scores predicted SICH (NINDS criteria) with good accuracy (ROC area> 0.7, Figure1). Only one score predicted SICH (NINDS criteria) with good accuracy (Figure2). Conclusion: We concluded that MRI-DRAGON presented the best predictive performance for SICH, and MRI may be more useful for selecting thrombolysis and endovascular treatment in acute ischemic stroke than CT.

OBJECTIVE: The presence of metabolic syndrome (MetS) is strongly associated with stroke and cardiovascular diseases. However, the relationship between MetS and the localization of atherosclerosis at various sites remains uncertain. In this study, in order to reveal the relevance of MetS to atherosclerosis at several sites, we investigated the relationships among vascular risk factors, asymptomatic cerebral infarction and atherosclerosis in the aorta and carotid and coronary arteries in adults without overtly symptomatic cerebrovascular or cardiovascular disease. METHODS: The subjects in this study included 2,759 Japanese participants (1,845 men and 914 women, mean age: 52 years) with no history of stroke or cardiovascular events. The diagnosis of MetS was made based on modifications to criteria obtained from the National Cholesterol Education Program Adult Treatment Panel. In all subjects, the presence of cerebral infarction in the extra-cranial carotid, coronary and aortic arteries was investigated using MRI, B-mode ultrasonography and CT. RESULTS: Of the 2,759 subjects, 796 (28.9%) fulfilled the criteria for MetS. The presence of MetS increased the odds ratio (OR) to 1.89 (95% confidence interval (CI): 1.35-2.65, p-value

Background Seasonal variation of stroke incidence has been reported in many countries. The present study was designed to elucidate seasonal and monthly variations in the incidence of subtypes of acute ischemic stroke and hypertensive hemorrhagic stroke using the Japanese Standard Stroke Registry Study (JSSRS) database, which is currently the world's largest hospital-based stroke database, accumulating records from 163 Japanese institutions. Methods Among 47,782 patients with acute stroke registered with JSSRS between 1998 and 2007, we selected 35,631 for analysis (patients with ischemic or hemorrhagic stroke of unknown etiology were excluded). A simple moving average was used to examine monthly variation of stroke incidence. We also examined seasonal variation of ischemic stroke subtypes. Results and Conclusions Monthly variation in incidence of all ischemic stroke was significant ( P P P P = .057). In contrast, cardioembolic stroke ( P P

Inositol hexakisphosphate kinase 2 (InsPThe specimens of spinal cords were obtained from mSOD1 Tg mice and age-matched wild-type mice. We investigated the expression of InsPThe gene expression levels of InsPThese findings suggest that InsP

Cilostazol, a pluripotent phosphodiesterase III-specific inhibitor with anti-platelet and vasculogenic effects, is useful for preventing recurrent brain vascular events, particularly in stroke patients with diabetes mellitus (DM). However, it is unclear whether cilostazol affects autoregulatory responses in small cerebral arteries. Thus, we investigated the effect of cilostazol on diabetic brain vasculopathy in a model of type II DM using male OLETF rats. OLETF rats were treated with either cilostazol (CG) or vehicle (VG) and subjected to microangiography with monochromatic synchrotron radiation to investigate middle cerebral artery (MCA) vasoreactivity following an injection of acetylcholine (Ach). Ach administration led to MCA diameter contraction in the VG, but MCA dilation in the CG. We also evaluated morphological changes in the small intracranial vessels and found that in the CG, the endothelial cell structure in the small artery was not destroyed. Moreover, protein levels of phosphorylated endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) were higher in each evaluated brain region in CG rats vs. VG rats. Our results suggest that cilostazol could potentially improve autoregulatory responses in the small cerebral arteries by increasing eNOS phosphorylation and VEGF expression in DM, and thus, may act as a neurovascular protectant.

In acute phase of ischemic stroke, as neuroprotective and neurogenerative role of granulocyte-colony stimulating factor(G-CSF), anti-apoptotic action, anti-inflammatory and anti-immune effect, and brain protective action against excitatory neurotoxicity have been reported. Several clinical trials in ischemic stroke patients using G-CSF have been carried out and reported the safety, improvement of clinical symptom, and reduction of infarct volume. But the efficacy of G-CSF administration in acute ischemic stroke has not been well proved. Further clinical studies with more patients, more uniform infarct size, and similar distributions of stroke subtype, are needed to clarify its effectiveness. Combined therapy with G-CSF and thrombolysis will be also expected as the next step of clinical trials.

Cerebral white matter lesions (WMLs) have been frequently observed on MRI in patients with migraine. We investigated characteristics of WMLs in migraine and tried to determine the relationship between its causal mechanism and arteriosclerosis.A head MRI was performed in juvenile migraine patients. The distributions of deep and periventricular WMLs were separately studied in the anterior and posterior circulation. Grading was conducted according to the Fazekas classification. Arteriosclerotic risk factors were identified, and their effects on WMLs were investigated.WMLs were observed in 85 (40.5%) of 210 patients in our hospital. This is significantly higher than the 10 (19.2%) of 63 patients in the control group (p0.01). WMLs were significantly observed on the anterior territory of the deep white matter (p0.01) and the posterior territory of the periventricular white matter (p0.05). Multivariable analysis revealed that the occurrence of WMLs was not related to arteriosclerotic risk factors, while migraine (p0.01) and aging (p0.05) were significant risk factors.While migraine was a risk factor of WMLs, its relationship with arteriosclerotic factors was weak. Accordingly, a mechanism other than arteriosclerosis may be involved.

Background and Purpose— The discrimination between paroxysmal and sustained (persistent or permanent) atrial fibrillation (AF) has not been considered in the approach to secondary stroke prevention. We aimed to assess the differences in clinical outcomes between mostly anticoagulated patients with sustained and paroxysmal AF who had previous ischemic stroke or transient ischemic attack. Methods— Using data from 1192 nonvalvular AF patients with acute ischemic stroke or transient ischemic attack who were registered in the SAMURAI-NVAF study (Stroke Management With Urgent Risk-Factor Assessment and Improvement-Nonvalvular AF; a prospective, multicenter, observational study), we divided patients into those with paroxysmal AF and those with sustained AF. We compared clinical outcomes between the 2 groups. Results— The median follow-up period was 1.8 (interquartile range, 0.93–2.0) years. Of the 1192 patients, 758 (336 women; 77.9±9.9 years old) and 434 (191 women; 77.3±10.0 years old) were assigned to the sustained AF group and paroxysmal AF groups, respectively. After adjusting for sex, age, previous anticoagulation, and initial National Institutes of Health Stroke Scale score, sustained AF was negatively associated with 3-month independence (multivariable-adjusted odds ratio, 0.61; 95% confidence interval, 0.43–0.87; P =0.006). The annual rate of stroke or systemic embolism was 8.3 and 4.6 per 100 person-years, respectively (multivariable-adjusted hazard ratio, 1.95; 95% confidence interval, 1.26–3.14) and that of major bleeding events was 3.4 and 3.1, respectively (hazard ratio, 1.13; 95% confidence interval, 0.63–2.08). Conclusions— Among patients with previous ischemic stroke or transient ischemic attack, those with sustained AF had a higher risk of stroke or systemic embolism compared with those with paroxysmal AF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01581502.

Elevating Akt activation is an obvious clinical strategy to prevent progressive neuronal death in neurological diseases. However, this endeavor has been hindered because of the lack of specific Akt activators. Here, from a cell-based high-throughput chemical genetic screening, we identified a small molecule SC79 that inhibits Akt membrane translocation, but paradoxically activates Akt in the cytosol. SC79 specifically binds to the PH domain of Akt. SC79-bound Akt adopts a conformation favorable for phosphorylation by upstream protein kinases. In a hippocampal neuronal culture system and a mouse model for ischemic stroke, the cytosolic activation of Akt by SC79 is sufficient to recapitulate the primary cellular function of Akt signaling, resulting in augmented neuronal survival. Thus, SC79 is a unique specific Akt activator that may be used to enhance Akt activity in various physiological and pathological conditions.

We present an unusual case of a patient with scrub typhus who developed acalculous cholecystitis, aseptic meningitis and mononeuritis multiplex. The patient was successfully treated with oral minocycline. To our knowledge, this is the first report of mononeuritis multiplex caused by scrub typhus.

Aim: Platelet aggregates with white blood cells (WBC-platelet complex) have recently been proposed as a marker of activated platelets, in addition to well-known molecular markers. We aimed to investigate the colocalization of activated platelets and WBC-platelet complex by means of flow cytometry, in patients with ischemic stroke.Methods: Eighty-six patients with cerebral infarction (CI) in the acute phase (58 males, 28 females; 65±14 years old) and 62 non-CI controls (23 males, 39 females; 53±14 years old) were registered. The appearance of WBC-platelet complex was quantified using 3-color flow cytometry.Results: The appearance rate of WBC-platelet complex was significantly higher in the CI group than in the controls. The appearance rate of WBC-platelet complex was significantly higher in atherothrombotic infarction (AT) than in lacunar infarction (LA) (p < 0.05). Furthermore, positive rates of both monocyte-platelet complex and granulocyte-platelet complex, but not lymphocyte-platelet complex, were significantly higher in the AT group than in the controls.Conclusion: We concluded that WBC-platelet complex, especially involving monocytes and granulocytes, is a novel marker of platelet activation in the acute phase of ischemic stroke, mainly in AT.

Renal dysfunction may be related to cerebral small-vessel disease. This study aimed to assess the relationship between mild renal dysfunction and various white matter hyperintensities on magnetic resonance imaging (MRI). A total of 2106 subjects (1368 men and 738 women; mean age, 56 ± 10 years) without a history of stroke were enrolled in the study. Kidney function was evaluated in terms of estimated glomerular filtration rate (eGFR), calculated using the relationship 194Cr(-1.094) × age(-0.287) × 0.739 (if female), where Cr is serum creatinine concentration. White matter hyperintensity on T2-weighted MRI was classified as deep and/or subcortical white matter hyperintensity (DSWMH), periventricular hyperintensity (PVH), or asymptomatic cerebral infarction (ACI). The prevalence of ACI, DSWMH, and PVH was significantly correlated with degree of eGFR reduction; in the subgroups with eGFR ≥ 90, 60∼89, and60 mL/min/1.73 m(2), the following prevalences were found: ACI, 7%, 6%, and 16%; DSWMH, 18%, 21%, and 37%; PVH: 7%, 10%, and 21%. The odds ratios for ACI, DSWMH, and PVH of eGFR60 mL/min/1.73 m(2) were significantly increased, to 2.11 (95% confidence interval [CI], 1.23-3.61; P = .006), 2.26 (1.53-3.34; P.001), and 2.81 (1.67-4.72; P.001), respectively. Our data indicate that mild renal dysfunction may be associated with an increase in cerebral small-vessel disease independent of hypertension.

A 73-year-old man was admitted with sudden right upper-limb weakness. He had a temporal headache on the left side and had a 4-month history of fever. Meandering of the left temporal artery (TA) with induration and high inflammatory responses (white blood cell count 22,500 per microliter, C-reactive protein 35.0 mg/dL, and elevated sedimentation rate [ESR] 80 mm/h) were observed. Glycometabolism and lipid metabolism were normal, and autoimmune antibodies were negative. Cultivation tests revealed no bacteria in either blood culture or cerebrospinal fluid. Brain magnetic resonance imaging (MRI) showed ischemic lesion in the left frontal lobe, while magnetic resonance angiography (MRA) and carotid ultrasonography showed unstable plaque lesions in the left extracranial internal carotid artery (ICA). According to reported criteria (age > 50 years, new onset of headache, abnormality of the TA, and raised ESR), we diagnosed giant cell arteritis (GCA) with acute ischemic stroke (IS) and gave the patient antithrombotic therapy (aspirin 100 mg, cilostazol 200 mg). After admission, hemiparesis progressed but fluctuated. Subsequent MRI showed new lesions in the left watershed area. MRA also showed vasospasm in the middle cerebral artery and C5 portion of the ICA. Considering the correlation with GCA pathophysiology, oral prednisolone therapy was administered. Steroid therapy has prevented stroke recurrence and improved the symptoms and vasospasm. We wish to emphasize that GCA can induce IS via vasospasm, and steroid therapy is recommended.

Inositol pyrophosphate diphosphoinositol pentakisphosphate is ubiquitously present in mammalian cells and contains highly energetic pyrophosphate bonds. We have previously reported that inositol hexakisphosphate kinase type 2 (InsP(6)K2), which converts inositol hexakisphosphate to inositol pyrophosphate diphosphoinositol pentakisphosphate, mediates apoptotic cell death via its translocation from the nucleus to the cytoplasm. Here, we report that InsP(6)K2 is localized mainly in the cytoplasm of lymphoblast cells from patients with Huntington disease (HD), whereas this enzyme is localized in the nucleus in control lymphoblast cells. The large number of autophagosomes detected in HD lymphoblast cells is consistent with the down-regulation of Akt in response to InsP(6)K2 activation. Consistent with these observations, the overexpression of InsP(6)Ks leads to the depletion of Akt phosphorylation and the induction of cell death. These results suggest that InsP(6)K2 activation is associated with the pathogenesis of HD.

The oxygen free radical scavenger edaravone is used in patients with acute ischemic stroke in Japan, but adverse reactions, especially decreased renal function, have raised concerns. To examine whether a patient's estimated glomerular filtration rate (eGFR) at admission can predict renal function deterioration after edaravone treatment, we retrospectively evaluated the effect of edaravone on eGFR in Japanese patients with acute ischemic stroke and chronic kidney disease (CKD). The baseline eGFR in the edaravone-treated group (73.5±20.3 mL/min/1.73 m(2); n=408) at admission was significantly (P.05) higher than that in the non-edaravone-treated group (51.9±25.2 mL/min/1.73 m(2); n=41). The change in eGFR after treatment was categorized into 3 grades: nonexacerbation (≤10%), 10%-30% exacerbation, and30% exacerbation. There was no significant difference in exacerbation grade between the edaravone-treated and non-edaravone-treated groups (χ(2) =3.134; P=.21). We next subdivided the edaravone-treated group according to eGFR at admission as either CKD (eGFR60 mL/min/1.73 m(2); n=111) and non-CKD (n=297). No significant decrease in eGFR was seen even in the edaravone-treated CKD group (most of whom were in stage 3 CKD). Decreased eGFR in stroke patients was found to be associated with stroke subtype (cardiogenic stroke), but not with infection. The present study demonstrates that eGFR at admission is not a good predictor of renal deterioration in edavarone-treated acute ischemic stroke patients, including those with stage 3 CKD.

A variety of human disorders, e.g., ischemic heart disease, stroke, kidney disease, eventually share the deleterious consequences of a common, hypoxic and oxidative stress pathway. In this review, we utilize recent information on the cellular defense mechanisms against hypoxia and oxidative stress with the hope to propose new therapeutic tools. The hypoxia-inducible factor (HIF) is a key player as it activates a broad range of genes protecting cells against hypoxia. Its level is determined by its degradation rate by intracellular oxygen sensors prolyl hydroxylases (PHDs). There are three different PHD isoforms (PHD1–3). Small molecule PHD inhibitors improve hypoxic injury in experimental animals but, unfortunately, may induce adverse effects associated with PHD2 inhibition, e.g., angiogenesis. As yet, no inhibitor specific for a distinct PHD isoform is currently available. Still, the specific disruption of the PHD1 gene is known to induce hypoxic tolerance, without angiogenesis and erythrocytosis, by reprogramming basal oxygen metabolism with an attendant decreased oxidative stress in hypoxic mitochondria. A specific PHD1 inhibitor might therefore offer a novel therapy against hypoxia. The nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) regulates the basal and inducible expression of numerous antioxidant stress genes. Disruption of its gene exacerbates oxidative tissue injury. Nrf2 activity is modulated by Kelch-like ECH-associated protein 1 (Keap1), an intracellular sensor for oxidative stress. Inhibitors of Keap 1 may prove therapeutic against oxidative tissue injury.

Objective Oxidative modification of carbohydrates and lipids enhances the formation of advanced glycation end products (AGEs), which are formed not only in hyperglycemia, but also in normoglycemia. In this study, we determined skin AGEs in patients with cerebral infarction. Patients and Methods We non-invasively measured skin autofluorescence (AF) levels in patients with chronic cerebral infarction (CCI; n=95), patients with silent brain infarction (SBI; n=40), and age-matched controls (n=34), using an AGE Reader. Results Skin AF levels in patients with CCI and SBI were significantly increased compared with those in the control group (2.06±0.38, 2.16±0.47 and 1.84±0.35, respectively). Angiotension receptor blocker (ARB) or statins had no significant effect on the level of advanced glycation in any of the groups. Conclusion Our data suggest that increased formation of AGEs may be an indicator of oxidative stress, not only in diabetes and renal failure, but also in chronic cerebral ischemia.

Objective: The intracardiac thrombus is associated with an increase in the risks of stroke and thromboembolism for primary prevention. However, it remains unclear in the setting of early management of patients with acute ischemic stroke/TIA. The purpose of this study was to clarify the impact of intracardiac thrombi on recurrent ischemic events in acute ischemic stroke/TIA patients with nonvalvular atrial fibrillation (NVAF). Methods: In the SAMURAI-NVAF study (an ongoing prospective, multicenter, observational study), 1192 acute ischemic stroke/TIA patients with NVAF were registered. Of these, the patients who underwent transesophageal echocardiography (TEE) and/or transthoracic echocardiography (TTE) during acute hospitalization were included. We evaluated the association between the prevalence of intracardiac thrombi and recurrent ischemic events (composite of ischemic stroke/TIA and systemic embolism) during hospital stay (median 29 days). Results: A total of 1091 patients (474 women, 77.6±9.9 y.o) were studied. Of these, 48 patients had intracardiac thrombus (4.4% [95% CI, 3.3-5.7%]). In acute hospital stay, 29 recurrent ischemic events (2.7% [1.9-3.8%]; 24 ischemic stroke, 3 TIA, and 2 systemic embolism) occurred. Patients with intracardiac thrombi had higher incidence of recurrent ischemic events than those without (12.5% versus 2.2%, p Conclusion: In acute ischemic stroke/TIA patients with NVAF, intracardiac thrombi are associated with risk of recurrent ischemic events. The evaluation of intracardiac thrombus should be considered in acute phase of ischemic stroke/TIA.

Background and purpose: The discrimination between paroxysmal and persistent atrial fibrillations (AF) has not been considered to guide secondary stroke prevention, because it remains unclear whether patients with persistent AF are at higher risk compared with paroxysmal AF, particularly in secondary prevention. We aimed to assess the differences in clinical outcomes between mostly anticoagulated patients with persistent vs. paroxysmal AF who had ischemic stroke or TIA. Methods: Using interim data of 1192 nonvalvular AF (NVAF) patients with acute ischemic stroke or TIA who were registered in the SAMURAI-NVAF study (an ongoing prospective, multicenter, observational study) to determine choice of anticoagulantion therapy and clinical outcomes, we divided patients into those with paroxysmal AF and those with persistent AF. We compared clinical outcomes between the 2 groups. Results: The median follow-up period was 1.0 year (IQR 0.3-2.0). Of the 1192 patients, 434 (191 women, 77.3±10.0 y.o.) and 758 (336, 77.9±9.9) were assigned to the paroxysmal AF group and persistent AF group, respectively. Of each group, 220 (50.7%) and 442 (58.3%) were anticoagulated with warfarin and 199 (45.9%) and 276 (36.4%) were so with non-vitamin K antagonist oral anticoagulant (NOAC) (p=0.004). As for primary outcomes, 30 (6.2%/person-year) and 78 (9.9) ischemic events, respectively [hazard ratio adjusted for sex, age, initial NIHSS, CHADS2 score, creatinine clearance, anticoagulation with warfarin (vs. NOAC) (HR) 0.65; 95% CI 0.42-0.98], and 18 (4.9%/person-year) and 31 (3.8) hemorrhagic events, respectively (HR 0.97, 0.52-1.75), occurred during follow-up. As for secondary outcomes, the person-year rate of ischemic stroke or TIA was 3.9% and 8.4%, respectively (HR 0.46, 0.27-0.76), that of intracranial hemorrhage was 1.6% and 1.7%, respectively (HR 0.97, 0.36-2.37), and that of death was 11.1% and 15.7%, respectively (HR 0.90, 0.64-1.26). Conclusions: Among patients with prior ischemic stroke or TIA, those with persistent AF had a higher risk of ischemic events, and ischemic stroke or TIA compared with those with paroxysmal AF. The prevention of progress to persistent AF from paroxysmal AF may be beneficial for secondary prevention in patients with NVAF.

We have developed a novel, non-toxic inhibitor of advanced glycation and oxidative stress, TM2002, devoid of effect on blood pressure. In transient focal ischemia, TM2002 significantly decreased infarct volume compared with vehicle (79.5 +/- 18.7 vs. 183.3 +/- 22.9 mm(3), p < 0.01). In permanent focal ischemia, TM2002 (2.79, 5.58, and 11.16 mg/kg twice a day) dose-dependently reduced infarct volume (242.1 +/- 32.3, 201.3 +/- 15.1, and 171.3 +/- 15.2 mm(3), respectively), and improved neurological deficits. Reduction of infarct volume is demonstrable, provided that TM2002 was administered within 1.5 h after the occlusion. To unravel TM2002's mechanism of action, we examined its in vitro effect on endoplasmic reticulum (ER) stress, using aortic smooth muscle cells isolated from ORP 150(+/-) mice and F9 Herp null mutated cells. Cell death induced by ER stress (tunicamycin or hypoxia) was dose-dependently prevented by TM2002. In vivo immunohistochemical study demonstrated a significant reduction of ORP- and TUNEL-positive apoptotic cells, especially in the penumbra. Inhibition of advanced glycation and oxidative stress was confirmed by a significantly reduced number of cells positive for advanced glycation end products and heme oxygenase-1. TM2002 reduced the levels of protein carbonyl formation in ischemic caudate. The efficacy of TM2002 is equivalent to that of a known neuroprotective agent, NXY-059. In conclusion, TM2002 significantly ameliorates ischemic cerebral damage through reduction of ER stress, advanced glycation, and oxidative stress, independently of blood pressure lowering. (c) 2007 Published by Elsevier B.V.

Hyperinsulinemia has been implicated in the development of diabetic nephropathy. In the present study we compared the renoprotective effects of the thiazolidinedione, pioglitazone (PGZ), to that of insulin in a hypertensive, obese, type II diabetic rat model. PGZ aggravated obesity and gave less glycemic control than insulin. However, renoprotection was markedly better with PZG compared to insulin as shown by lower proteinuria, improved renal function, and less histological evidence of diabetic glomerular and tubulointerstitial lesions. PZG and insulin both reduced renal accumulation of pentosidine and oxidative stress to a similar extent. In contrast, PGZ but not insulin suppressed enhanced transforming growth factor-beta (TGF-beta) expression. We further confirmed in cultured rat proximal tubular cells that insulin enhanced TGF-beta mRNA expression and protein production. Our results identify hyperinsulinemia and the attendant increase of TGF-beta expression as potential therapeutic targets in diabetes independent of glycemic control. This confirms prior clinical evidence that PZG provides renoprotection in obese, diabetic patients with nephropathy.

The rising tide of chronic kidney disease (CKD), especially diabetic nephropathy, has become a worldwide catastrophe. However, therapeutic options to prevent or retard the progression of CKD still remain very limited. The understanding of its molecular mechanisms and the delineation of tools able to modify them are thus of critical importance. The discovery that some antihypertensive agents inhibiting the renin-angiotensin system, such as angiotensin II type 1 receptor blockers, protect the kidney opens new therapeutic perspectives. In this article, we focus on their renoprotective actions beyond blood pressure lowering.

As altered blood flow in the cerebral perforating arteries (PA) might be related to development of cerebral white matter hyperintensities, we examined whether the hemodynamic relationship of the PA and middle cerebral artery (MCA) is altered in rat models of diabetes, compared with normal rats and a rat model of sinoatrial denervation (blood pressure fluctuation model).We used microangiography with monochromatic synchrotron radiation to measure the diameters of the PA and MCA at 4.5 μm resolution in five groups of rats: (i) Long-Evans Tokushima Otsuka (LETO); (ii) Otsuka Long-Evans Tokushima Fatty (a model of type 2 diabetes with obesity); (iii) LETO with sinoaortic denervation (LETO + SAD); (iv) F344; and (v) F344 + streptozotocin (a model of type 1 diabetes).Compared with LETO, Otsuka Long-Evans Tokushima Fatty rats showed a significant reduction in the diameter of both PA and MCA, though the PA/MCA diameter ratio was unchanged. In contrast, compared with LETO, LETO + SAD rats showed an increased MCA diameter, and the PA/MCA diameter ratio was decreased. Compared with F344 rats, the MCA diameter was increased in F344 + streptozotocin rats, and the PA/MCA diameter ratio was decreased. Scatter diagrams showed that the diameters of the PA and MCA were essentially independent of each other in the two types of diabetic models.PA were consistently visualized at high resolution by means of microangiography using synchrotron radiation. The present results show that rat diabetic models exhibit changes in PA diameter and PA/MCA diameter ratio, which might be related to the development of diabetes-associated cerebral white matter hyperintensities.

To verify the usefulness in selection of antiplatelet agent based on the platelet functional assays on the secondary prevention of ischemic stroke.Platelet functional assays were performed twice for acute ischemic stroke patients at hospitalization and 1 month after. An antiplatelet agent was administered based on the results of initial assay. The alterations of platelet aggregation by antiplatelet agent were evaluated in the second assay, and the patients were subsequently divided into inhibited and invariance groups. The relationship between incidence of recurrent ischemic or hemorrhagic stroke and the alterations of platelet aggregation by each selected antiplatelet agent was assessed.Of the 585 consecutive patients, 124 were enrolled in the present study. Recurrent ischemic stroke was seen in 6 (5.3%) and 2 (18.2%) patients in the inhibited and invariance groups during the study period, respectively. In patients who were observed for more than 12 months, recurrent ischemic stroke was seen in 4 (5.0%) and 2 (33.3%) patients in the inhibited and invariance groups, respectively (p = 0.009).We indicated that selection of the optimum antiplatelet agent based on the platelet functional assays for each individual patient may contribute to a reduction in the incidence of recurrence of ischemic stroke.

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 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.

A 51-year-old man was admitted to our hospital complaining of preceding throbbing headache and tonic convulsions. Headache and convulsive seizure disappeared and his consciousness recovered to alert within 2 hours after onset. Neurological examination showed no abnormal findings. Laboratory examinations revealed high low-density lipoprotein cholesterol (179 mg/dL), renin (42 ng/mL/hour), aldosterone (265 pg/mL), noradrenaline (1031 pg/mL), and dopamine (79 pg/mL). In brain magnetic resonance imaging (MRI), fluid-attenuated inversion recovery, but not the diffusion-weighted image, showed high signal intensities in white matter in bilateral occipital, parietal, and frontal lobes, with no stenotic changes on magnetic resonance angiography. In addition, the diffusion coefficient of focal lesions was elevated. Decreasing blood flow velocity and separated lumens in the right renal artery trunk were shown by renal artery ultrasonography. Enhanced computed tomography and renal angiography showed right renal partial infarction and isolated stenosis in the right renal artery, accompanied by thrombosed false lumen. No stenotic changes were seen in other peripheral arteries. These findings seemed incompatible with renal dissection and fibromuscular dysplasia, Takayasu's arteritis, and polyarteritis nodosa. Our diagnosis was posterior reversible encephalopathy syndrome (PRES) induced by renal hypertension due to renal artery dissection. To improve the renal artery stenosis and secondary hypertension, we performed plain balloon angioplasty, in addition to administering antihypertensive and lipid-lowering medications. After angioplasty, hypertension and high signal intensity at brain MRI were clearly improved. We would like to emphasize that renal artery angioplasty should be considered as an option for patients with PRES and malignant hypertension.

A 73-year-old man presented with continuous hemichoreic movement of right arm and leg and with dyskinesia in his tongue. Magnetic resonance image (MRI) showed no ischemic lesion within the basal ganglia, but magnetic resonance angiography (MRA) and carotid duplex ultrasonography showed the left internal carotid occlusion and 80% stenosis in the right common carotid artery. Tc-99m-ECD-SPECT showed hypoperfusion of the frontal lobe, temporal lobe, parietal lobe, basal ganglia and thalamus. A trial of haloperidol had no effect; therefore, the right carotid artery stenting was performed. Hypoperfusion in the left internal carotid artery area was improved by cross flow from the right side, and his hemichorea gradually improved. This result supports the notion that hypoperfusion-related hemichorea may occur, even in the absence of cerebral ischemia.

A 64-year-old man presented with diplopia, muscle weakness, a pulmonary nodule and mediastinal widening on a chest radiograph. He was diagnosed with clinical stage IIIA (T2aN2M0) lung cancer. His neurological symptoms worsened following the initiation of thoracic radiation therapy (60 Gy) and chemotherapy. A diagnosis of myasthenia gravis (MG) was confirmed with a repetitive nerve stimulation test that showed a waning pattern, and a positive edrophonium test, although neither anti-acetylcholine receptor antibodies nor anti-muscle-specific tyrosine kinase antibodies were detected. The ptosis and limb muscle weakness improved with prednisolone and acetylcholinesterase inhibitor treatment, and a partial response of the lung cancer to chemoradiotherapy was obtained. However, the ptosis and limb muscle weakness worsened again following a recurrence of the lung cancer. The herein described case, in which lung cancer and MG occurred and recurred simultaneously, suggests that MG can develop as a paraneoplastic syndrome of lung cancer.

Rationale Anticoagulants are widely used to prevent recurrence of ischemic stroke in patients with nonvalvular atrial fibrillation, but in some patients, they also cause bleeding, particularly intracranial hemorrhage. One of the independent predictors of intracerebral hemorrhage is the presence of cerebral microbleeds (CMBs); a high incidence of intracerebral hemorrhage is reported in warfarin-treated patients with multiple CMBs. Longitudinal study suggested that the presence of CMBs at baseline is a predictor of new CMBs in warfarin-treated patients. However, there has been no study on the progression of CMBs in patients receiving the non–vitamin K antagonist oral anticoagulants (NOACs). Aims This study tests the hypothesis that the incidence of hemorrhagic stroke is lower in patients receiving NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) than in those receiving warfarin, and this difference reflects the difference in the effects of warfarin and NOACs on the progression of CMBs. Design We will enroll 200 patients with at least 1 CMB detected by 1.5 T magnetic resonance imaging ( T 2 ∗ -weighted imaging) at baseline and who have received NOACs or warfarin for at least 12 months. Primary end point is the proportion of subjects with an increased number of CMBs at month 12 of treatment with NOACs or warfarin. If the results of this study support the efficacy of NOACs for preventing increase of CMBs, this would be of great interest to domestic and overseas clinicians, in view of the potential therapeutic impact, including that on primary prevention of ischemic stroke.

外科的手術あるいは内視鏡検査前などにおける抗血小板薬休薬の至適期間を,血小板凝集の面から検討した.手術・検査のために抗血小板薬を一時中止した患者22例(アスピリン9例,チクロピジン13例)を対象とし,休薬前,休薬3日,7日,14日目に比濁法にて血小板最大凝集率を求めた.その結果,アスピリン群では休薬前に対し休薬3日後より有意に凝集能が亢進し(14.0±8.5% vs 48.1±31.2%; p

For multi-institution clinical research on cerebrovascular disease, the standardization of MR imaging conditions is required. Firstly, the magnetic field strength must be the same in all the facilities, and it is at least necessary for a chronological sequence of observations of the same patient to be conducted on the same machine at the same facility. Further, the angle and width of brain slices in MRI must be the same. Secondly, in addition to T1WI, T2WI and FLAIR, T2WI is recommended for detection of micro-bleeding in the brain. Thirdly, perivascular spaces, number and areas of infarcts, and deep white matter and periventricular white matter hyperintensities must be evaluated according to specified criteria. Such standardization of MR imaging among different institutions should provide high-quality evidence to elucidate the pathophysiology of cerebrovascular disease and to develop therapeutic strategies.

Long-term bilateral common carotid occlusion (BCCAO) in rats induces brain hypoperfusion and structural injury, and could have relevance as a model of vascular dementia in which cortical metabolism is reduced. The present study was designed to assess whether phosphate-related energy compounds and blood supplies are markedly affected by KCI-induced cortical spreading depression (CSD), which leads to metabolic and cerebral blood flow changes in rats with chronic BCCAO, by means of near-infrared spectroscopy and phosphorus magnetic resonance spectroscopy. Male Wistar rats were divided into 4 groups: BCCAO for 1 week (n = 6) and 4 weeks (n = 15), and sham operation for 1 week (n = 7) and 4 weeks (n = 7). The phosphocreatine (Pcr) index (PCr/PCr+Pi) and intracellular pH (pHi) were measured pre-CSD, just after KCl application, and at 20 and 40 minutes after CSD. Brains were evaluated by histology with hematoxylin and eosin and immunohistochemical reaction for glial fibrillary acidic protein (GFAP). Rapid signal changes of oxy-, deoxy-, and total hemoglobin were observed in all KCl-applied brains. The PCr index and pHi values in BCCAO were not different than those in control rats. The percentage of vacuolated area in the optic tract and percentage values of GFAP-positive area in the frontoparietal cortex were significantly increased in BCCAO. The generation of CSD was seen in regions of cortical gliosis induced by BCCAO, and severe energy exhaustion did not occur during or after CSD. Our results may suggest that the functional interaction of neurons and glia is sustained even in brain tissue where the metabolic state of neurons is impaired and astrocytes are proliferated.

It is unclear whether asymptomatic cerebral infarction (ACI) is associated with an increased risk of stroke. We therefore evaluated the number of ACI, perivascular hyperintensity (PVH) and deep subcortical white matter hyperintensity (DSWMH) on MRI in 468 subjects with ACI, who consist of in healthy elderly persons and in patients with a first stroke. The number of ACI (less than 10mm), perivascular space, the grading of PVH and DSWMH were significantly increased year by year. The grading of PVH was increased only in subjects with hypertension, although the number of ACI was increased in subjects with or without hypertension. No effects of total cholesterol and triglyceride on the number of ACI and the grading of PVH and DSWMH were observed. In subjects with ACI, annual incidence of clinical stroke was significantly higher in patients with a first stroke (6.9%) than in healthy elderly persons (1.7%). Although the number of ACI was significantly aggravated year by year in spite of using hypertensive, hyperlipidemic and anti-platetet agents, the grading of PVH and DSWMH were aggravated only in patients given no medications. These results indicate that the management of risk factors is important for patients with ACI, as same as in patients with stroke.

Backgound and Purpose: Recently, three non-vitamin K antagonist oral anticoagulants (NOACs) became available for patients with nonvalvular atrial fibrillation (NVAF) in Japan. We aimed to determine 3-month outcomes in ischemic stroke/TIA patients receiving NOACs or warfarin from a multicenter prospective registry (SAMURAI-NVAF registry, NCT01581502). Methods: Among 1,191 acute ischemic stroke /TIA patients enrolled between September 2011 and March 2014, we studied 916 patients (389 women, 77±10 y) who took oral anticoagulants (OACs) after index stroke and completed 3-month follow-up survey. Primary outcome measures were ischemic events, including recurrent stroke/TIA and thromboembolism, and major bleedings events, such as fatal bleeding and/or symptomatic bleeding in a critical area or organ according to the International Society on Thrombosis and Haemostasis statement. We assessed the incidence and clinical factors associated with primary outcomes within 90 days after initiating OACs. Results: NOACs were given for 370 patients (126 women, 74±9 y; dabigatran 168, rivaroxaban 183 and apixaban 19) and warfarin for 546 (263 women, 79±10 y). NOAC users had lower scores of CHADS2 (median 3 in NOAC, 4 in warfarin, p Conclusion: The 3-month incidence of ischemic events in stroke/TIA patients with NVAF was approximately 4% in both NOAC and warfarin users. Intracranial hemorrhage was relatively infrequent in NOAC users.

Background and Purpose: We aimed to assess whether prior antithrombotic therapy affects initial neurological severity and functional outcome in acute ischemic stroke patients with non-valvular atrial fibrillation (NVAF). Methods: Patients with NVAF who were admitted within 7 days after ischemic stroke onset from 2011 to 2014 were enrolled from the register of a prospective, multicenter, observational study (the SAMURAI-NVAF study). Patients receiving novel oral anticoagulants at onset were excluded from the study. They were classified into 3 groups: the non-WF group, patients without prior warfarin; the iWF group, those on warfarin with initial PT-INR below the target range; the sWF group, those on warfarin with initial PT-INR within or above the target range. They were also divided into patients without prior antiplatelet agents (the non-AP group) and those with (the AP group). Initial neurological severity was measured by NIHSS score. Poor functional outcome was defined by mRS 3-6 at 3 months of onset. Results: Of 1000 patients studied, 713, 221 and 66 were assigned to the non-WF group, the iWF group and the sWF group, respectively. Of all, 245 were assigned to the AP group, mainly taking aspirin (202 patients). On multivariate analysis, the sWF group (vs. the non-WF group) (standardized regression coefficient [β], -0.23; p Conclusions: Prior sufficient warfarinization was associated with mild neurological severity and favorable outcome in acute ischemic stroke patients with NVAF, whereas prior insufficient warfarinization and prior antiplatelet therapy were not.

Background and purpose: The impact of albuminuria on clinical outcomes in acute cardioembolic stroke is not fully investigated. We assessed whether high spot urine albumin/creatinine ratio (ACR) was associated with clinical outcomes in acute stroke with non-valvular atrial fibrillation (NVAF). Methods: From 2011 to 2014, we enrolled acute ischemic stroke/TIA patients with NVAF in the SAMURAI-NVAF study, which is a multicenter, observational study. Patients with complete ACR values were included in the analysis. They were divided into the N (normal, ACR < 30mg/g) and the H (high, ACR ≥ 30mg/g) groups. Clinical outcomes were neurological deterioration (an increase of NIHSS ≥1 point during the initial 7 days) and poor outcome (mRS of 4-6 at 3 months). Results: Of 558 patients (328 men, 77±10 y) who were included, 271 and 287 were assigned to the H group and the N group, respectively. As compared with patients in the N group, those in the H group were more frequently female (52 vs 31%, p < 0.001) and older (80±10 vs 75±10 y, p < 0.001). On admission, patients in the H group more frequently had diabetes (28 vs 17%, p = 0.003), less frequently had paroxysmal AF (68 vs 57%, p = 0.009), had higher levels of SBP (157±28 vs 151±24 mmHg, p = 0.003), NIHSS score (11 vs 5, p < 0.001), CHA2DS2-VASc score (6 vs 5, p < 0.001), plasma glucose (141±62 vs 132±41 mg/dL, p = 0.04), and brain natriuretic peptide (348±331 vs 259±309 pg/mL, p = 0.002), and had lower levels of hemoglobin (13±2 vs 14±2 g/dL, p = 0.02), and estimated glomerular filtration ratio (eGFR) (60±24 vs 66±20 mL/min/1.73m2 p = 0.002). On imaging studies, patients in the H group more frequently had large infarct (29 vs 20 %, p = 0.02) and culprit artery occlusion (64 vs 48%, p < 0.001). Neurological deterioration (14 vs 4%, p < 0.001) and poor outcome (49 vs 24%, p < 0.001) were more frequently observed in the H group. On multivariate regression analysis adjusted for significant confounders and reperfusion therapy, the H group was associated with neurological deterioration (OR 2.43; 95% CI 1.14-5.5; p = 0.02) and poor outcome (OR 2.75; 95% CI 1.45-5.2; p = 0.002), although eGFR was not significantly related to either. Conclusion: High ACR, a marker of albuminuria, was independently associated with unfavorable outcomes in acute stroke patients with NVAF.

We describe the case of a 72-year-old man who presented with dementia that had progressed rapidly over a few months. Laboratory analysis of blood and cerebrospinal fluid (CSF) showed no abnormalities, with the exception of a slightly increased CSF protein level. Results of routine magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) and magnetic resonance angiography (MRA) were unremarkable. However, detailed neuroimaging studies including contrast-enhanced T1-weighted MRI and conventional angiography revealed a superior sagittal sinus (SSS) dural arteriovenous fistula (DAVF). After endovascular embolization and surgical interruption of all arteries feeding the DAVF, the dementia reversed. We should be aware of the possibility of DAVF as the cause of rapidly progressive dementia even if routine MRI reveals no or only minimal abnormality.