Temporal Relationship between Impairment of Cerebellar Motor Learning and Deterioration of Ataxia in Patients with Cerebellar Degeneration.

Ataxia and impaired motor learning are both fundamental features in diseases affecting the cerebellum. However, it remains unclarified whether motor learning is impaired only when ataxia clearly manifests, nor it is known whether the progression of ataxia, the speed of which often varies among patients with the same disease, can be monitored by examining motor learning. We evaluated motor learning and ataxia at intervals of several months in 40 patients with degenerative conditions [i.e., multiple system atrophy (MSA), Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3), SCA6, and SCA31]. Motor learning was quantified as the adaptability index (AI) in the prism adaptation task and ataxia was scored using the Scale for the Assessment and Rating of Ataxia (SARA). We found that AI decreased most markedly in both MSA-C and MSA-P, moderately in MJD, and mildly in SCA6 and SCA31. Overall, the AI decrease occurred more rapidly than the SARA score increase. Interestingly, AIs remained normal in purely parkinsonian MSA-P patients (n = 4), but they dropped into the ataxia range when these patients started to show ataxia. The decrease in AI during follow-up (dAI/dt) was significant in patients with SARA scores < 10.5 compared with patients with SARA scores ≥ 10.5, indicating that AI is particularly useful for diagnosing the earlier phase of cerebellar degeneration. We conclude that AI is a useful marker for progressions of cerebellar diseases, and that evaluating the motor learning of patients can be particularly valuable for detecting cerebellar impairment, which is often masked by parkinsonisms and other signs.

Tandem internal models execute motor learning in the cerebellum.

In performing skillful movement, humans use predictions from internal models formed by repetition learning. However, the computational organization of internal models in the brain remains unknown. Here, we demonstrate that a computational architecture employing a tandem configuration of forward and inverse internal models enables efficient motor learning in the cerebellum. The model predicted learning adaptations observed in hand-reaching experiments in humans wearing a prism lens and explained the kinetic components of these behavioral adaptations. The tandem system also predicted a form of subliminal motor learning that was experimentally validated after training intentional misses of hand targets. Patients with cerebellar degeneration disease showed behavioral impairments consistent with tandemly arranged internal models. These findings validate computational tandemization of internal models in motor control and its potential uses in more complex forms of learning and cognition.

CSF cytokine profile in MOG-IgG+ neurological disease is similar to AQP4-IgG+ NMOSD but distinct from MS: a cross-sectional study and potential therapeutic implications.

OBJECTIVE: To evaluate cerebrospinal fluid (CSF) cytokine profiles in myelin oligodendrocyte glycoprotein IgG-positive (MOG-IgG+) disease in adult and paediatric patients. METHODS: In this cross-sectional study, we measured 27 cytokines in the CSF of MOG-IgG+ disease in acute phase before treatment (n=29). The data were directly compared with those in aquaporin-4 antibody-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) (n=20), multiple sclerosis (MS) (n=20) and non-inflammatory controls (n=14). RESULTS: In MOG-IgG+ disease, there was no female preponderance and the ages were younger (mean 18 years, range 3-68; 15 were below 18 years) relative to AQP4-IgG+ NMOSD (41, 15-77) and MS (34, 17-48). CSF cell counts were higher and oligoclonal IgG bands were mostly negative in MOG-IgG+ disease and AQP4-IgG+ NMOSD compared with MS. MOG-IgG+ disease had significantly elevated levels of interleukin (IL)-6, IL-8, granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor, interferon-γ, IL-10, IL-1 receptor antagonist, monocyte chemotactic protein-1 and macrophage inflammatory protein-1α as compared with MS. No cytokine in MOG-IgG+ disease was significantly different from AQP4-IgG+ NMOSD. Moreover many elevated cytokines were correlated with each other in MOG-IgG+ disease and AQP4-IgG+ NMOSD but not in MS. No difference in the data was seen between adult and paediatric MOG-IgG+ cases. CONCLUSIONS: The CSF cytokine profile in the acute phase of MOG-IgG+ disease is characterised by coordinated upregulation of T helper 17 (Th17) and other cytokines including some Th1-related and regulatory T cells-related ones in adults and children, which is similar to AQP4-IgG+ NMOSD but clearly different from MS. The results suggest that as with AQP4-IgG+ NMOSD, some disease-modifying drugs for MS may be ineffective in MOG-IgG+ disease while they may provide potential therapeutic targets.

Does Treatment of Impaired Glucose Tolerance Improve Cardiovascular Outcomes in Patients with Previous Myocardial Infarction?

PURPOSE: We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT). METHODS: This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure. RESULTS: The age, ratio of males, and HbA1C were 65 vs. 65 years, 86 vs. 87%, and 5.6 vs. 5.5% in the groups with and without voglibose, respectively. Voglibose improved IGT; however, Kaplan-Meier analysis showed no significant between-group difference with respect to cardiovascular events [12.5% with voglibose vs. 10.1% without voglibose for the primary endpoint (95% confidence interval, 0.82-1.86)]; there were no significant differences in secondary endpoints. CONCLUSION: Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT00212017.

Cerebral aneurysm neck diameter is an independent predictor of progressive occlusion after stent-assisted coiling.

BACKGROUND: Some intracranial aneurysms treated by stent-assisted coiling (SAC) with incomplete occlusion undergo progressive occlusion (PO) during follow-up period. We analyzed the predictors for the occurrence of PO. METHODS: Among 74 cerebral aneurysms treated by SAC using the Enterprise or Neuroform stents from 2010 to 2015, we included 43 aneurysms with occlusion grade of neck remnant (NR, n = 36) or residual aneurysm (RA, n = 7) at the post-procedure. We defined PO as improvement in occlusion grade from RA to NR, or from NR or RA to complete occlusion on angiographic follow-up imaging at 6 months after the procedure. We analyzed the independent predictors for PO using a multivariate logistic regression model and receiver operating characteristic (ROC) curve analysis. RESULTS: Forty-three aneurysms were analyzed, with mean volume embolization ratio of 30.3 ± 6.7%. Twenty aneurysms (47%) achieved PO. Univariate analysis found that the median neck diameter of the aneurysms was smaller in aneurysms with PO than others. Multivariate logistic regression analysis also found that the odds ratio of neck diameter of the aneurysm for PO was 0.44 (95% CI, 0.19-0.82, p < 0.01). Moreover, ROC curve analysis for PO found that the optimal cut-off value of the neck diameter was 5.5 mm, with a sensitivity of 95%, specificity of 57% (p < 0.01). CONCLUSIONS: Incompletely occluded aneurysms with a neck diameter of 5.5 mm or less might be more likely to develop PO within 6 months after SAC by using Enterprise or Neuroform stents.

[Development of Deep Venous Thrombosis Shortly after Neurological Surgery].

Little is known about the incidence and characteristics of deep venous thrombosis(DVT)developing shortly after neurological surgery. Lower extremity venous ultrasound scanning was performed before and after surgery, and retrospective data of 157 surgical cases, including endovascular surgery(42.0%), craniotomy(28.7%), burr hole(24.2%), and shunt(3.2%), were evaluated. DVT that had not been pre-operatively observed was discovered in five cases of surgery(five patients, 3.2%)on the day following the surgery, and it was asymptomatic in all cases. One patient was diagnosed with pulmonary thromboembolism as a complication. No difference in characteristic factors was observed between the presence and absence of DVT development. In addition, DVT was detected on preoperative examinations in 10 cases of surgery(10 patients, 6.4%). On the basis of these results, ambulation on the first postoperative day is considered mostly safe. On the other hand, taking into account the increase in the number of patients with DVT and the possibility that a thrombus present in calf veins propagates toward the proximal side, pre-and post-operative screening tests should be performed more often.

Renal function on admission modifies prognostic impact of diuretics in acute heart failure: a propensity score matched and interaction analysis.

Although intravenous diuretics have been mainstay drugs in patients with acute heart failure (AHF), they have been suggested to have some deleterious effects on prognosis. We postulated that renal function may modify their deleterious effects in AHF patients. The study population consisted of 1094 AHF patients from three hospitals. Renal dysfunction (RD) was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 on admission, and the cohort was divided into a high-dose furosemide (≥100 mg/48 h) and low-dose furosemide group according to the amount of intravenous furosemide used within 48 h from admission. In the whole cohort, in-hospital mortality rate was higher in the high-dose furosemide group than the low-dose furosemide group (12.5 vs. 6.6 %, respectively, P = 0.001). However, this difference in the in-hospital mortality rates was significant only in the RD subgroup (15.6 vs. 7.0 %, respectively, P < 0.001), and not in the non-RD subgroup (2.5 vs. 5.9 %, respectively, P = 0.384). Propensity score-matched analysis was performed to evaluate the impact of high-dose furosemide on prognosis. After propensity score matching, high-dose furosemide was not associated with in-hospital mortality (OR 1.25, 95 % CI 0.73-2.16, P = 0.408). However, there was a qualitative difference in OR for in-hospital mortality between AHF with RD (OR 1.77, 95 % CI 0.96-3.28, P = 0.068) and without RD (OR 0.23, 95 % CI 0.05-1.10, P = 0.064), and there was a significant interaction between eGFR and prognostic impact of high-dose furosemide (P for OR interaction = 0.013). An inverse relationship was observed between eGFR and OR for in-hospital death in the group treated with high-dose furosemide (decreasing OR with better eGFR). The deleterious effect of diuretics was significantly modified with renal function in AHF. This association may be one reason for poorer prognosis of AHF patients complicated with renal impairment.

Moderate vasomotor response to acetylcholine provocation test as an indicator of long-term prognosis.

The acetylcholine (ACh) provocation test (ACh-test) is used for the diagnosis of vasospastic angina (VSA). However, subjects often show a moderate spasm (MS) response for which diagnosis of VSA is not definitive, and the clinical significance of this response is unknown. We assessed moderate coronary vasomotor response to the ACh test as an indicator of long-term prognosis. A total of 298 consecutive patients who underwent the ACh test for suspected VSA were retrospectively investigated. Coronary spasm severity after intracoronary administration of isosorbide dinitrate was evaluated by measuring epicardial coronary artery diameter reduction after ACh injection. Patients were divided into three groups according to the diameter reduction during the ACh test: severe spasm (SS) showing ≥75 % diameter reduction, MS showing ≥50 % diameter reduction, and others (N). In Kaplan-Meier analysis, the major adverse cardiac event (MACE) rates with a median follow-up of 4.6 years were significantly worse in SS (11.1 %) and MS (8.5 %) than N (1.9 %), (SS vs N; P = 0.009, MS vs N; P = 0.029). Significant difference in MACE rates was not observed between SS and MS (P = 0.534). Cox regression analysis revealed that MS remained an independent predictor of MACE after adjustment for other confounders (HR: 7.18, 95 % CI 1.42-36.4, P = 0.017). Patients with MS by ACh test had a cardiac event rate comparable with that of patients with SS and significantly worse than that of patients with normal vasomotor responses.

Double balloon protection during carotid artery stenting for vulnerable carotid stenosis reduces the incidence of new brain lesions.

BACKGROUND: The use of distal filter protection alone is associated with a high risk of ischemic complications when vulnerable carotid stenosis is treated by carotid artery stenting (CAS). Double balloon protection, a combination of distal balloon protection and proximal balloon occlusion, can be utilized. We assessed the outcome and complications of the double balloon protection method for vulnerable carotid stenosis. METHODS: Among 130 patients who underwent CAS from 2009 to 2014, we enrolled the following patients: those whose target lesion was vulnerable as evaluated by MRI, i.e., a signal ratio of plaque to posterior cervical muscle on T1-weighted images before CAS of ≥1.5, and those who underwent diffusion-weighted imaging (DWI) studies within 48 h after the procedure. Ninety patients were enrolled. We investigated DWI findings of the double balloon protection group compared with those of the simple distal balloon protection and distal filter protection groups. RESULTS: Sixty-four patients (71 %) underwent double balloon protection, 15 patients (17 %) simple distal balloon protection, and 11 patients (12 %) distal filter protection. Symptomatic embolic complications and new lesions on DWI after CAS were significantly less common in patients undergoing double balloon protection compared to distal balloon protection or distal filter protection (0 % vs. 20 %, 9 %, P < 0.01, and 30 % vs. 67 %, 82 %, P < 0.01, respectively). Logistic regression analysis also identified the odds ratio of double balloon protection for new lesions on DWI after CAS of 0.23 (95 % confidence interval: 0.07-0.70, P < 0.01) compared to simple distal protections. CONCLUSIONS: In the patients who underwent CAS for vulnerable carotid stenosis, double balloon protection was an independent significant factor associated with a reduction in the risk of new lesions on DWI after the procedure compared to conventional distal protections.

Carperitide Is Associated With Increased In-Hospital Mortality in Acute Heart Failure: A Propensity Score-Matched Analysis.

BACKGROUND: Carperitide (α-human A-type natriuretic peptide) has been used for more than one-half of all acute heart failure (AHF) patients in Japan. However, its clinical effectiveness is not well documented. METHODS: We retrospectively identified AHF patients presenting with acute onset or worsening of symptoms and admitted to 1 of the 3 participating hospitals. Propensity score-matched analysis was performed. The primary end point was in-hospital mortality. RESULTS: Of all of the AHF patients included in this study, 402 (38.7%) were treated with carperitide, and in-hospital mortality rate for the total cohort was 7.6%. We matched 367 pairs of patients treated with and without carperitide according to propensity score. In this matched cohort, treatment with carperitide was associated with in-hospital mortality (odds ratio [OR] 2.13, 95% confidence interval [CI] 1.17-3.85; P = .013). Potentially more harmful effects were observed in elderly patients (OR 2.93, 95% CI 1.54-5.91). CONCLUSIONS: Carperitide was significantly associated with increased in-hospital mortality rate in AHF patients. Our results strongly suggest the necessity for well designed randomized clinical trials of carperitide to determine its clinical safety and effectiveness.

A novel mutation of PDE8B Gene in a Japanese family with autosomal-dominant striatal degeneration.

BACKGROUND: Autosomal-dominant striatal degeneration is a rare autosomal-dominant neurodegenerative movement disorder characterized by slowly progressive parkinsonism. Recently, a mutation of the cyclic nucleotide phosphodiesterase 8B gene was reported to be a causal gene mutation of this disease. METHODS: We report on the clinical characteristics of 2 patients of a Japanese family with autosomal-dominant striatal degeneration and the result of gene mutation analysis of this family. RESULTS: Clinical features of the patients are slowly progressive parkinsonism and brain MRI showing high signal intensity in T2-weighted images in the striatum. We found a heterozygous nonsense mutation in the first exon of cyclic nucleotide phosphodiesterase 8B gene, which is predicted to disrupt all important functional domains of the cyclic nucleotide phosphodiesterase 8B protein. CONCLUSIONS: This family is the second family with autosomal-dominant striatal degeneration after the first German family, confirming that cyclic nucleotide phosphodiesterase 8B gene is the causative gene for this disease.

Risk factors for rehospitalization in heart failure with preserved ejection fraction compared with reduced ejection fraction.

Although there have been several studies regarding heart failure with preserved ejection fraction (HFpEF), investigations of the risk factors for readmission of Japanese patients with HFpEF remain scarce. Therefore, our goal was to identify the risk factors for readmission of Japanese patients with heart failure (HF), particularly those with HFpEF. We analyzed 310 patients who were hospitalized for the first time with HF. Preserved EF was defined EF ≥50 %, and reduced EF (rEF) was EF <50 %. The study endpoint was readmission for HF after discharge. Medical history, vital signs, electrocardiograms, chest radiographs, blood tests and echocardiograms were compared between patients with HFpEF and with HFrEF. Among the 142 patients who had HFpEF, 43 reached the endpoint within 1 year. Multivariate analysis revealed depression (HR: 7.185), high brain natriuretic peptide (BNP) levels at discharge (HR: 1.003), and dilated inferior vena cava (HR: 1.100) as independent risk factors for readmission. In contrast, 39 of the 168 patients with HFrEF reached the endpoint. Risk factors for readmission of HFrEF patients were low sodium (HR: 0.856), high blood urea nitrogen (HR: 1.045), high BNP levels at discharge (HR: 1.003) and absence of beta-blocker prescription (HR: 0.395). In conclusion, our study suggests that the predictors of HF readmission differ between HFpEF and HFrEF patients.

[A case of Guillain-Barré syndrome with severe pain successfully controlled with acetaminophen, gabapentin, and parenterally infused fentanyl].

We presented a case of an 8-year-old boy with Guillain-Barré syndrome characterized by severe intractable pain in the soma and lower extremities, which appeared 2 weeks after a febrile cold. At his first visit to our hospital, he could not stand or walk because of the severe pain, and muscle weakness and absence of deep tendon reflexes were observed. Guillain-Barré syndrome was diagnosed on the basis of cerebrospinal fluid study results, nerve conduction velocity, and spinal cord magnetic resonance imaging. His pain was scored as a five on a six-point visual analog scale, and it persisted despite routine supportive therapy. The pain was successfully controlled with parenterally infused fentanyl. It is suspected that opioid analgesics are useful for severe pain control in patients with Guillain-Barré syndrome.

Synthesis, structures, and luminescence properties of interconvertible Au(I)2Zn(II) and Au(I)3Zn(II) complexes with mixed bis(diphenylphosphino)methane and D-penicillaminate.

The reaction of the digold(I) complex [Au2(dppm)(D-pen)2](2-) ([1](2-); dppm = bis(diphenylphosphino)methane and D-pen = D-penicillaminate) with Zn(2+) in a 1:1 ratio gave the heterometallic Au(I)2Zn(II) trinuclear complex [Au2Zn(dppm)(D-pen)2] ([3]), in which the Zn(2+) ion is coordinated by [1](2-) in an N2O2S2 octahedral geometry with the trans(O) configuration, forming an 8-membered Au2ZnS2P2C metalloring. A similar reaction using the newly prepared and crystallographically characterized trigold(I) complex [Au3(dppm)2(D-pen)2](-) ([2](-)) produced the Au(I)3Zn(II) tetranuclear complex [Au3Zn(dppm)2(D-pen)2](+) ([4](+)), in which the Zn(2+) ion is coordinated by [2](-) in a similar octahedral geometry to form a Au3ZnS2P4C2 12-membered metalloring. Complex [3] was converted to [4](+) by treatment with [Au2(dppm)2](2+) in a 2:1 ratio, whereas [4](+) reverted to [3] upon treatment with a mixture of [Au(d-pen)2](2-) and Zn(2+) in a 1:1 ratio, indicative of the facile insertion/removal of the [Au(dppm)](+) moiety with retention of the geometry of the trans(O)-[Zn(D-pen-N,O,S)2](2-) unit. An analogous interconversion that requires the insertion/removal of the [Au(dppm)](+) moiety was also recognized between [1](2-) and [2](-). NMR spectroscopy revealed that [4](+) is in equilibrium with [3] and [Au2(dppm)2](2+) in solution, the ratio of which is largely dependent on the solvent polarity. The luminescence properties of these complexes were also investigated, revealing the importance of the intramolecular aurophilic interaction, as well as the Zn(II) coordination, for enhancement of the emission quantum efficiencies.

Differences in action of atorvastatin and ezetimibe in lowering low-density lipoprotein cholesterol and effect on endothelial function: randomized controlled trial.

BACKGROUND: The aim of this study was to compare the effect on endothelial function of increasing statin dose to add-on ezetimibe in patients with coronary artery disease (CAD) already treated with statin. METHODS AND RESULTS: Two-hundred and forty-three patients with CAD and low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dl even after treatment with atorvastatin (10 mg) were prospectively randomized to the ezetimibe addition (10mg) group (A10E10; n=117) or to the double atorvastatin dose (to 20 mg; A20; n=133) group for 12 weeks. Primary endpoint was change in endothelial function measured by logarithmic-scale reactive hyperemia index (L_RHI). After treatment, high-sensitivity C-reactive protein (hs-CRP) and all lipids except triglyceride and high-density lipoprotein cholesterol were significantly reduced in both groups. The mean percent changes in LDL-C for the A10E10 and A20 groups were -25.8% and -9.1%, respectively (P<0.001). L_RHI increased from 0.47 to 0.62 in the A20 group (P<0.001), but not in the A10E10 group (from 0.45 to 0.48, P=0.399). Absolute change in L_RHI was significantly higher in the A20 than A10E10 group (0.02±0.29 vs. 0.16±0.27, P<0.001). CONCLUSIONS: Statin and ezetimibe have different effects on endothelial function independent from LDL-C-lowering effects.

Prognostic implications of chronic kidney disease and anemia after percutaneous coronary intervention in acute myocardial infarction patients.

Anemia is a common complication of chronic kidney disease (CKD), and a few studies suggest that both CKD and anemia have a marked impact on the prognosis of patients with cardiovascular disease. We retrospectively analyzed the prevalence of CKD and anemia in 312 patients with acute myocardial infarction (AMI). The patients were divided into four groups according to the presence of CKD and anemia. Chronic kidney disease was defined as estimated glomerular filtration rate <60 ml/min/1.73 m(2), and anemia was defined according to the World Health Organization definition. Of 312 AMI patients, 166 (53.2%) had CKD and 87 (27.8%) had anemia. A powerful relationship was observed between both CKD and anemia and major adverse cardiac and cerebrovascular events (MACCE) or death by any cause. After adjustment for comorbidities, the hazard ratio (HR) for MACCE was significantly higher in the anemia-only group (HR 5.42, 95% confidence interval (CI) 1.38-21.27, P = 0.015), the CKD-only group (HR 6.4, 95% CI 2.09-19.58, P = 0.001), and the CKD and anemia group (HR 11.61, 95% CI 3.65-36.89, P < 0.001). With respect to death by any cause, the HR was significantly higher in the CKD-only group (HR 2.68, 95% CI 1.02-7.02, P = 0.045) and the CKD and anemia group (HR 4.40, 95% CI 1.56-12.43, P = 0.005). One-half of the patients with AMI had CKD as well. Furthermore, when anemia coexisted with CKD, these conditions had a multiplicative amplification effect on the risk of MACCE and death by any cause in patients with AMI.

Myocarditis in a pediatric case of pandemic 2009H1N1 influenza.

We report a 6-year-old boy with no major disease history or allergic conditions initially presented with pneumonia, progressed to acute respiratory distress syndrome and acute myocarditis caused by pandemic 2009H1N1 influenza diagnosed with RT-PCR testing, successfully managed with mechanical ventilation and percutaneous cardiopulmonary support system. Marked transient elevation of IgE in acute phase of the disease and the subsequent diagnosis of atopic asthma in our patient suggested a possible role of an underlying allergic condition in the clinicopathological process. Critically ill 2009H1N1-infected patient with acute respiratory failure should carefully be physiologically monitored together with serial assessment of biomarkers aiming at a favorable cardiac outcome by giving the timely diagnosis and intervention.

Asymptomatic cerebral findings on 3-Tesla MRI in patients with severe carotid artery stenoses.

BACKGROUND AND PURPOSE: Small vessel diseases (SVDs) are often asymptomatic. However, SVDs significantly influence the prognosis in patients with large vessel diseases (LVDs). We investigated asymptomatic cerebral findings on 3-Tesla MRI in patients with severe carotid artery (CA) stenoses, compared to peoples without a past history of neurological disorders, including strokes. METHODS: We retrospectively analyzed the prevalences of various asymptomatic cerebral findings which were intracerebral hemorrhages (ICHs), cortical superficial siderosis, ventricular dilatation (Evans' index) and SVDs including cerebral microbleeds (CMBs), lacunar infarctions (LIs), deep white matter hyperintensities (WMHs), periventricular hyperintensities (PVHs). The prevalence of each finding was compared using multivariate logistic regression models with adjustment for stroke risk factors. RESULTS: We evaluated the findings in 54 patients with severe CA stenosis treated by stenting (CA stenosis group) and 200 adults with health screening tests of the brain and no past history of neurological disorders (control group). Multivariate analyses adjusted for age ≥ 65 years old, female gender, hypertension, hyperlipidemia, diabetes mellitus, alcohol consumption, and smoking index revealed that the prevalences of severe PVHs, severe deep WMHs, asymptomatic deep ICHs, and asymptomatic LIs were significantly higher in the CA stenosis group than the control group. However, there were no significant differences in the prevalences of CMBs, or the remaining asymptomatic findings described above. CONCLUSIONS: With pathological differences between SVD and LVD, asymptomatic SVDs except CMBs and deep ICHs often co-exists severe CA stenosis as a presentative LVD.

Current state of symptomatic aortic valve stenosis in the Japanese elderly.

BACKGROUND: There have been few reports regarding treatment selection and prognosis of symptomatic aortic valve stenosis (AS) in the elderly in Japan. METHODS AND RESULTS: Sixty-one patients hospitalized between January 2000 and December 2007 for symptomatic severe AS were investigated. The average observation period was 27 months. Thirty-seven patients (61%) were diagnosed with AS for the first time on hospitalization. Thirty-six patients had onset of symptoms within 1 month before admission. Thirty-six patients received aortic valve replacement (group S) and 25 received medical therapy (group M). The patients in group M were older than those in group S (84.1 ± 5.3 years vs. 74.2 ± 4.6 years, P<0.001). Maximum flow velocity measured by echocardiography was lower in group M (4.5 ± 0.3 m/s vs. 4.9 ± 0.5 m/s, P<0 .01), but there was no difference in valve area between the 2 groups (0.62 ± 0.19 cm² vs. 0.57 ± 0.15 cm², P=0.12). One-year mortality rate derived from the Kaplan-Meier curve was higher in group M than group S (53.1% vs. 6.4%, respectively). On multivariate analysis, the only independent favorable prognostic factor was aortic valve replacement (HR: 0.02, 95%CI: 0.01-0.15, P<0.01). CONCLUSIONS: Medical therapy is often selected for treatment of symptomatic AS in the elderly, but the prognosis is very poor. Symptomatic severe aortic stenosis should be treated surgically, or with transcatheter aortic valve implantation in cases with high surgical risk.

Prevalence and prognostic implications of pre-diabetic state in patients with heart failure.

BACKGROUND: Diabetes mellitus (DM) is a risk factor of poor prognosis in patients with heart failure (HF). The prevalence and prognostic impact of the pre-diabetic state, however, are not well understood. METHODS AND RESULTS: One hundred and thirty-six consecutive patients admitted due to HF were included in this prospective study. The 75-g oral glucose tolerance test (OGTT) was performed in all patients without known DM, and patients were classified into normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and DM groups. Forty-two of the 136 patients had previously been diagnosed with diabetes. Of the remaining 94 patients without known diabetes, 35 (37.2%) patients were classified as NGT, 9 (9.6%) as having IFG, 37 (39.4%) were classified as having IGT, and 13 (13.8%) were newly diagnosed with DM. During follow-up, patients with DM or IGT had significantly lower major adverse cardiac and cerebrovascular event (MACCE)-free rates than NGT patients (P=0.006, P=0.036, respectively). IFG, however, was not significantly related to increased MACCE risk. The presence of IGT (hazard ratio [HR], 4.51; P=0.011) and DM (HR, 4.74; P=0.005) were independent predictors of MACCE even after multivariate analysis. CONCLUSIONS: IGT and DM contribute to adverse prognosis in patients with HF. It is feasible to perform diabetes screening using OGTT in patients with HF for risk stratification.