Association of Age-Related Spontaneous Internal Jugular Vein Reflux with Cognitive Impairment and Incident Dementia.

BACKGROUND: It remains unclear whether changes in the venous circulation contribute to cognitive decline. OBJECTIVE: This study aimed to clarify whether the spontaneous jugular vein reflux (JVR) is associated with cognitive impairment and incident dementia. METHODS: Patients with any evidence of cerebral vessel disease on magnetic resonance imaging (MRI) were consecutively enrolled between October 2015 to July 2019. We employed carotid duplex sonography to measure the internal jugular vein (IJV). The subjects were classified into two groups based on the degree of JVR on either side: none, mild (JVR(-) group) and moderate, severe (JVR (+) group) JVR. They underwent both the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment-Japanese (MoCA-J) global tests. Their cognitive status was prospectively assessed until March 2023. RESULTS: 302 patients with an MMSE score ≥24 underwent duplex sonography of the IJV. Among them, 91 had spontaneous JVR on either side. Both MMSE and MoCA-J were significantly lower in patients with JVR (+) group than in the JVR (-) group. After the adjustment for risk factors and MRI findings, intergroup differences in MoCA-J remained significant. Among the cognitive subdomains, median executive function and memory scores were significantly lower in the JVR (+) group than in the JVR (-) group. During the median 5.2-year follow-up, 11 patients with incident dementia were diagnosed. Patients with severe JVR were significantly more likely to be diagnosed with dementia (log-rank test, p = 0.031). CONCLUSIONS: Spontaneous IJV reflux especially severe JVR, was associated with global cognitive function, and potentially with incident dementia.

Remote ischemic conditioning for acute ischemic stroke part 2: Study protocol for a randomized controlled trial.

Background: Remote ischemic conditioning (RIC) refers to the application of repeated short periods of ischemia intended to protect remote areas against tissue damage during and after prolonged ischemia. Aim: We aim to evaluate the efficacy of RIC, determined by the modified Rankin Scale (mRS) score at 90 days after stroke onset. Design and methods: This study is an investigator-initiated, multicenter, prospective, randomized, open-label, parallel-group clinical trial. The sample size is 400, comprising 200 patients who will receive RIC and 200 controls. The patients will be divided into three groups according to their National Institutes of Health Stroke Scale score at enrollment: 5-9, mild; 10-14, moderate; 15-20, severe. The RIC protocol will be comprised of four cycles, each consisting of 5 min of blood pressure cuff inflation (at 200 mmHg or 50 mmHg above the systolic blood pressure) followed by 5 min of reperfusion, with the cuff placed on the thigh on the unaffected side. The control group will only undergo blood pressure measurements before and after the intervention period. This trial is registered with the UMIN Clinical Trial Registry (https://www.umin.ac.jp/: UMIN000046225). Study outcome: The primary outcome will be a good functional outcome as determined by the mRS score at 90 days after stroke onset, with a target mRS score of 0-1 in the mild group, 0-2 in the moderate group, and 0-3 in the severe group. Discussion: This trial may help determine whether RIC should be recommended as a routine clinical strategy for patients with ischemic stroke.

Brain Natriuretic Peptide Is a Powerful Predictor of Outcome in Stroke Patients with Atrial Fibrillation
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BACKGROUND: Since stroke patients with nonvalvular atrial fibrillation (NVAF) have poor outcomes in general, the prediction of outcomes following discharge is of utmost concern for these patients. We previously reported that brain natriuretic peptide (BNP) levels were significantly higher in NVAF patients with larger infarcts, higher modified Rankin Scale (mRS) score, and higher CHADS2 score. In the present study, we evaluated an array of variables, including BNP, in order to determine significant predictors for functional outcome in patients with NVAF after acute ischemic stroke (AIS). METHODS: A total of 615 consecutive patients with AIS within 48 h of symptom onset, admitted to our hospital between April 2010 and October 2015, were retrospectively searched. Among these patients, we enrolled consecutive patients with NVAF. We evaluated the mRS score 3 months after onset of stroke and investigated associations between mRS score and the following clinical and echocardiographic variables. Categorical variables included male sex, current smoking, alcohol intake, hypertension, diabetes mellitus, dyslipidemia, coronary artery disease, peripheral artery disease, use of antiplatelet drugs, anticoagulants, or tissue plasminogen activator (tPA), and infarct size. Continuous variables included age, systolic blood pressure (SBP), diastolic blood pressure, hemoglobin, creatinine, D-dimer, brain natriuretic peptide (BNP), left atrial diameter, left ventricular ejection fraction (EF), and early mitral inflow velocity/diastolic mitral annular velocity (E/e'). We also analyzed the association of prestroke CHADS2, CHA2DS2-VASc, and R2CHADS2 scores, and National Institutes of Health Stroke Scale (NIHSS) score on admission with mRS score 3 months after the onset of stroke. Patients were classified into 2 groups according to mRS score: an mRS score ≤2 was defined as good outcome, an mRS score ≥3 was defined as poor outcome. To clarify the correlations between categorical or continuous variables and mRS score, uni- and multivariate logistic regression models using the stepwise variable selection method were applied. RESULTS: Among 157 patients with NVAF after AIS, 63.7% were male and the mean age was 75.9 years. In univariate regression analysis, poor outcome (mRS score ≥3) was associated with use of tPA, infarct size, age, SBP, BNP, EF, and NIHSS score. In multivariate regression analysis, BNP levels (odds ratio [OR] 6.40; 95% confidence interval [CI] 1.26-32.43; p = 0.0235) and NIHSS score (OR 2.87; 95% CI 1.84-4.47; p < 0.001) were significantly associated with poor outcome (mRS score ≥3) after adjusting for use of tPA, infarct size, age, BNP, EF, and NIHSS score. CONCLUSIONS: Apart from NIHSS score, BNP was a very useful predictor for long-term outcomes of patients with NVAF after AIS.
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Brachial-ankle pulse wave velocity is associated with 3-month functional prognosis after ischemic stroke.

BACKGROUND AND AIMS: Brachial-ankle pulse wave velocity (baPWV) is a good measure of arterial stiffness and is associated with risk of future vascular events. The present study aimed to examine whether baPWV can also predict 3-month functional outcome after stroke. METHODS: This hospital-based study included 327 consecutive patients with acute ischemic stroke and in whom baPWV was measured during hospitalization. We defined good and poor functional outcomes as a modified Rankin Scale score of <3 and ≥ 3 at 3 months, respectively, after initial stroke. RESULTS: Patients with poor outcomes were significantly older (73.1 versus 66.3 years, p < 0.001) and more likely to have extracranial carotid arterial stenosis (29.5% versus 13.1%, p < 0.001), atrial fibrillation (21.0% versus 11.3%, p = 0.020), history of coronary artery disease (20.0% versus 11.7%, p = 0.042), and high baPWV value (22.84 versus 19.48 m/s, p < 0.001). Irrespective of patients' age, sex, baseline risk factors, initial stroke severity, and stroke etiology, baPWV was consistently higher in patients with poor outcome than those with good outcome. Multivariate analysis revealed that baPWV >23.11 m/s, calculated from the receiver-operating characteristic curve, had an independent predictive value for poor functional outcome (odds ratio, 1.51; 95% confidence interval, 1.08-2.11; p = 0.016). CONCLUSIONS: BaPWV measured during the acute phase of stroke can independently predict 3-month functional prognosis. We suggest that baPWV should be performed as part of the early stroke work-up to identify patients suffering from severe stroke-related disability.

Persistence of non-vitamin K antagonist oral anticoagulant use in Japanese patients with atrial fibrillation: A single-center observational study.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) show a favorable balance between efficacy and safety compared with warfarin for patients with non-valvular atrial fibrillation (NVAF). In "real-world" practice, however, NOAC adherence and persistence among patients are not clear. The aim of this study is to evaluate NOAC and warfarin persistence in Japanese patients with NVAF who newly started these drugs. METHODS: We retrospectively studied 401 patients with NVAF who had newly started NOACs during the first 18 months after our hospital adopted their use (197 dabigatran, 107 rivaroxaban, 102 apixaban) and 200 patients with NVAF who had newly started warfarin during the same period. The endpoint was drug discontinuation for each drug. RESULTS: During the follow-up period (up to a maximum of 24 months), 113 (28%) patients who had newly started NOACs and 33 (17%) patients who had newly started warfarin discontinued the drug. The persistence rates of patients prescribed NOACs was lower than that of patients prescribed warfarin at 3, 6, and 12 months (85% versus 93%, 79% versus 88%, and 70% versus 82%, respectively). One-tenth of patients who had newly started NOACs discontinued the drug by their own decision. Drug adverse events, worsening renal dysfunction, and patient desire were the major causes of NOAC discontinuation. CONCLUSIONS: The rate of persistence of prescribed NOACs was significantly lower than that of warfarin in Japanese patients with NVAF.

Prolonged QTc interval predicts poststroke paroxysmal atrial fibrillation.

BACKGROUND AND PURPOSE: Paroxysmal atrial fibrillation (PAF) is often difficult to detect in patients with acute ischemic stroke. We aimed to assess the predictive value of a prolonged QT interval corrected for heart rate (QTc) in PAF detection after acute ischemic stroke. METHODS: We enrolled 972 patients with acute ischemic stroke consecutively extracted from our observational stroke registry system. Exclusion criteria were as follows: (1) AF on the initial 12-lead ECG (n=171); (2) previously diagnosed PAF (n=47); and (3) the use of a cardiac pacemaker (n=10). Of the 972 patients, 744 (mean age, 67.6 years; men, 62.6%) were eligible for analysis. The clinical characteristics and 12-lead ECG findings of the patients with and without PAF were compared, and multiple logistic regression analysis was performed to identify predictors of poststroke PAF. RESULTS: The poststroke cardiac work-up yielded 69 (9.3%) de novo PAF cases among the 744 patients. The QTc interval was significantly longer in patients with PAF than in those without PAF (436 versus 417 ms; P<0.001). Each 10-ms increase in the QTc interval was associated with an increased risk of PAF after multivariate adjustments (odds ratio, 1.41; 95% confidence interval, 1.24-1.61; P<0.001). The optimal threshold value of QTc interval calculated by a receiver-operating characteristic curve was 438 ms, and the area under the curve was 0.73 in this data set. CONCLUSIONS: The QTc interval prolongation is potentially a strong and useful predictor for poststroke PAF.

Two soluble isoforms of receptors for advanced glycation end products (RAGE) in carotid atherosclerosis: the difference of soluble and endogenous secretory RAGE.

BACKGROUND: Advanced glycation end products (AGEs) promote atherosclerosis through binding to their receptor, RAGE. Since soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) may suppress AGEs-RAGE signaling, we examined the usefulness of sRAGE and esRAGE as biomarkers of early-stage atherosclerosis. METHODS: Serum sRAGE and esRAGE levels were measured in 284 subjects with no history of atherothrombotic diseases. The subjects were divided into high-sRAGE and low-sRAGE groups and high-esRAGE and low-esRAGE groups based on respective median values. We investigated the relationships between these parameters and the following factors: number of metabolic components, maximum intima-media thickness of the common carotid artery (IMT Cmax), carotid plaque calcification, and asymptomatic cerebral white matter lesions. RESULTS: The low-sRAGE and low-esRAGE groups exhibited significantly more components of metabolic syndrome than the high-sRAGE and high-esRAGE groups, respectively. IMT Cmax was significantly higher in the low-sRAGE and low-esRAGE groups. Low-sRAGE levels were significantly associated with carotid plaque calcification. Multiple linear regression analysis identified body mass index (BMI), age, and high-sensitivity C-reactive protein as determinants of sRAGE, whereas only BMI was identified as a determinant of esRAGE. CONCLUSIONS: We demonstrated that sRAGE and esRAGE are associated with atherosclerotic risk factors in early-stage atherosclerosis, suggesting that their levels evolve in correlation with those of metabolic components and inflammation. Interestingly, low-sRAGE and esRAGE levels are associated with high IMT Cmax, but only low-sRAGE levels were associated with carotid plaque calcification. Thus, sRAGE and esRAGE may reflect different aspects of atherosclerosis in its early stage.

Brain natriuretic peptide in acute ischemic stroke.

Elevated serum brain natriuretic peptide (BNP) levels are associated with cardioembolic stroke mainly because of atrial fibrillation (AF). However, the mechanisms of increased serum BNP levels are hitherto unclear. We aimed to identify the factors associated with increased BNP levels in patients with acute ischemic stroke. We measured serum BNP levels in consecutive patients aged 18 years or older. Stroke subtypes were classified using the Trial of ORG 10172 in Acute Stroke Treatment criteria. Categorical variables included age, sex, smoking status, alcohol consumption status, hypertension, diabetes mellitus, dyslipidemia, coronary artery disease (CAD), AF, antiplatelet therapy, and anticoagulant therapy. Continuous variables included hemoglobin, creatinine (Cr), ß-thromboglobulin, platelet factor 4, thrombin-antithrombin complex, and d-dimer levels. We further determined the relationship between serum BNP and intima-media thickness, left ventricular ejection fraction, size of infarction, National Institutes of Health Stroke Scale score on admission, and modified Rankin Scale (mRS) score at discharge. Of the 231 patients (mean age, 71 ± 12 years) with acute ischemic stroke (AIS), 36% were women. Serum BNP levels significantly correlated with CAD, AF, Cr, mRS, and cardioembolism (CE) (Dunnett method, P = .004). BNP levels were significantly higher in patients with larger infarcts, higher mRS scores, and higher CHADS2 scores. The levels were higher in patients with larger infarcts, higher mRS scores at discharge, and higher CHADS2 scores among AF patients.

Modification of the sampling algorithm for reverse Monte Carlo modeling with an insufficient data set.

A new sampling method for reverse Monte Carlo (RMC) modeling has been developed to constitute a reasonable structural model with insufficient experimental data. Another merit of this method is its very low computational cost because the algorithm uses only the three nearest atomic coordinations in moving a selected atom. In order to test the method, RMC modeling with this algorithm was carried out for the scattering data of NaCl melts. The partial pair distribution functions obtained by the RMC modeling had no spikes or atomic aggregation in the cutoff distance region and agreed well with experimental data.

A case of adenoid cystic carcinoma presenting as Garcin's syndrome without mass formation.

Adenoid cystic carcinoma (ACC) is a malignant neoplasm that commonly arises in the major or minor salivary gland and usually forms mass lesions. Here, we report a case of ACC involving a 56-year-old man, who displayed right multiple cranial nerve palsies with ipsilateral severe facial pain but not any mass formation. Right submaxillary gland biopsy after repeated challenges at last revealed the primary focus of ACC with perineural invasion and without lymph node metastasis. The neurological manifestations were considered to be attributed to the perineural spread of ACC. It is extremely rare for ACC to show Garcin's syndrome without mass formation.

Packing structure of chains and rings in an expanded liquid Se80Te20 mixture near the semiconductor to metal transition.

X-ray scattering measurements of an expanded liquid Se(80)Te(20) mixture in the temperature range between 300 and 1000 °C and at pressures of 10, 200, and 1600 bar have been carried out. The reverse Monte Carlo simulation and Voronoi-Delaunay void analyses have been applied to clarify the relationship between the voids and chain geometries in the intermediate scale near the semiconductor to metal (SC-M) transition at 800 °C under 200 bar accompanied by a shrinkage of molar volume. The structure of the liquid mixture can be envisaged in terms of a packing of covalently bonded chains and interstitial voids. The thermal expansion leads to a decrease in the number of chains around a chain and is compensated for by empty spaces (voids). The packing density of helical chains decreases and so voids supported by chains increase with rising temperature. At high temperature the shortening of chains and frequent transfer of lone pair electrons on Se (or Te) atoms cause modification of the helical chain to ring and zigzag chain conformations. The stacking of zigzag chains, joined to layers above 800 °C, leads to the formation of metallic domains separated by voids. The shrinkage of molar volume near the SC-M transition arises through the progressive filling of the voids around chains with (Se, Te)(5, 6, 7, 8) rings.

Metabolic syndrome and its components as risk factors for first-ever acute ischemic noncardioembolic stroke.

BACKGROUND: Metabolic syndrome (MetS) has been studied as a cardiovascular risk factor. We evaluated MetS and its individual components as risk factors for acute ischemic noncardioembolic stroke (AINS). METHODS: The relationships of AINS with MetS and its components were analyzed in 200 patients with first-ever AINS and 200 age-matched control subjects. RESULTS: Patients with AINS had a higher MetS prevalence than control subjects (45.5% v 26.5%, P < .001). On logistic regression analysis, the adjusted odds ratio (OR) for MetS as a risk factor for AINS was 2.39 (95% confidence interval [CI] 1.14-4.98, P = .021). The AINS risk increased as the number of MetS components increased. Hypertension (OR 3.21, 95% CI 1.48-6.94, P = .003) and fasting hyperglycemia (OR 2.73, 95% CI 1.53-4.87, P = .001) were particularly significant risk factors among MetS components for AINS. CONCLUSION: MetS is an independent risk factor for AINS. Stroke risk increased as the number of MetS components increased. Hypertension and hyperglycemia were particularly significant components as risk factors for AINS.

Quasielastic neutron scattering investigation of motion of water molecules in n-propyl alcohol-water mixture.

The dynamics of water molecules in the n-propyl alcohol-water mixtures is investigated by using quasielastic neutron scattering measurements. The dynamic structure factor S(Q,E) obtained from incoherent scattering of hydrogen atoms of water is fitted with jump diffusion and relaxing cage models. The diffusion constant obtained from the relaxing cage model, which gives better fitting with S(Q,E), shows better agreement to the experimental value than that of jump diffusion model. The dependence of translational relaxation time tau(T)(Q) and stretched exponent beta(T)(Q) on the fraction of hydrophobic hydrating water molecules in the solution is discussed.

[QuantiFERON: an early diagnostic tool for cerebral tuberculosis].

Two cases (a 33-year-old woman and a 34-year-old man) were diagnosed as having cerebral tuberculosis. Case 1 was tuberculoma with miliary tuberculosis complicating cranial nerve palsies, and case 2 was tuberculous meningitis. Early diagnosis was difficult, because smear and PCR were negative. Culture was finally positive after several weeks. QuantiFERON were positive prior to the culture results in both cases. This reaction suggested tuberculous infection. QuantiFERON is useful for diagnosing cerebral tuberculosis at an early stage.

[Juvenile-onset multiple brain infarcts localized in the posterior circulation: a case report].

We report a 37-year-old male patient with multiple brain infarcts due to arterial lesions localized in the posterior circulation, who developed a paramedian pontine infarct on the left side. He had been treated as schizophrenia for 20 years. A cranial CT performed one year before showed old small infarcts in the territories of the bilateral thalamo-perforating and left thalamo-geniculate arteries and the right posterior inferior cerebellar artery. The vertebral and basilar arteries were small in diameter on MRI and MR angiography(MRA). Cerebral angiography revealed a narrow smooth basilar artery. In addition, the P2 segments of the bilateral posterior cerebral arteries were markedly narrow with irregular walls. Carotid arteriograms were normal and no atherosclerosis was found. The nature of these arterial lesions remains unknown in this case. Even if MRA shows vertebrobasilar artery hypoplasia, a known congenital risk factor of a posterior circulation infarct, we must rule out a possibility that some arterial pathology is going on.