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In this randomized, double-blind, placebo-controlled study, we investigated the effects of collagen peptides (CP) containing high concentrations of prolyl-hydroxyproline and hydroxyprolyl-glycine on the advanced glycation end products (AGEs) levels in the skin and subcutaneous blood vessel walls. Thirty-one individuals aged 47–87 years were randomly assigned to receive either 5 g/day fish-derived CP or a placebo for 12 weeks. Body and blood compositions and AGEs levels were measured at the beginning and end of the study. No adverse events were observed, and both groups’ blood and body compositions did not change significantly. However, the CP group had significantly lower AGEs levels and a slightly lower insulin resistance index (HOMA-R) than the placebo group. In addition, the % changes in AGEs and HOMA-R levels were positively and strongly correlated in both groups. These findings suggest that fish-derived CP may be effective in reducing AGEs levels and improving insulin resistance.

Casein hydrolysate has been shown to improve arterial stiffness as estimated by brachial-ankle pulse wave velocity (baPWV) in untreated hypertensive patients. Facial pigmentation is associated with atherosclerosis, both of which are supposed to be modulated by tissue accumulation of advanced glycation end products (AGEs). However, effects of casein hydrolysate on facial pigmentation and AGEs remain largely unknown. This randomized double-blind placebo-controlled trial evaluated whether and how casein hydrolysate improves facial pigmentation in 80 nonhypertensive Japanese patients. Study participants were randomly assigned to receive either active tablets containing casein hydrolysate or placebo for 48 weeks. Facial pigmentation area, baPWV, and skin accumulation levels of AGEs were evaluated by Robo Skin Analyzer RSA50S II, volume-plethysmographic apparatus, and AGE Reader, respectively, at baseline and at the end of the intervention. Treatment with casein hydrolysate, but not placebo significantly reduced triglycerides and facial pigmentation area. There were significant differences of changes in triglycerides, facial pigmentation area, skin accumulation levels of AGEs, and baPWV between the two groups. Furthermore, changes in triglycerides and skin accumulation levels of AGEs were positively and independently associated with those in facial pigmentation area, whereas changes in baPWV were not. This study suggests that casein hydrolysate reduces facial pigmentation area in nonhypertensive participants partly by decreasing skin accumulation levels of AGEs. Clinical-Trials.gov ID: UMIN000027675.

BACKGROUND Several feasibility studies and a randomized, controlled, multicenter trial have demonstrated the safety and efficacy of unilateral transcranial magnetic resonance-guided focused ultrasound (FUS) lesioning of the ventral intermediate thalamic nucleus in treating essential tremor. OBJECTIVE To evaluate the safety and efficacy of FUS thalamotomy in a Japanese patient cohort through a prospective, multicenter, single-arm confirmatory trial. METHODS A total of 35 patients with disabling refractory essential tremor underwent unilateral FUS thalamotomy and were followed up for 12 post-treatment months. Safety was measured as the incidence and severity of treatment-related adverse events. Efficacy was measured as the tremor severity and quality of life improvements using the Clinical Rating Scale for Tremor and Questionnaire for Essential Tremor. RESULTS The mean skull density ratio (SDR) was 0.47. There was a significant decrease in the mean postural tremor score of the treated hand from baseline to 12 mo by 56.4% (95% CI: 46.7%-66.1%; P

Background We assessed cases of incidental unruptured intracranial aneurysm (UIA) discovered on screening magnetic resonance angiography to identify hemodynamic and atherosclerotic risk factors. Methods and Results The data of 1376 healthy older subjects (age range, 31–91 years) without cerebro‐ or cardiovascular diseases who underwent brain magnetic resonance angiography as part of a medical checkup program at a health screening center were examined retrospectively. We looked for an increase in classical risk factors for UIAs (age, sex, hypertension, and smoking) and laboratory data related to lifestyle diseases among subjects with UIAs. Brachial‐ankle pulse wave velocity, central systolic blood pressure, radial augmentation index, and carotid flow pulsatility index were also compared between those with and without UIAs. We found UIAs in 79 (5.7%) of the subjects. Mean age was 67.1±9.0 years, and 55 (70%) were women. Of the 79 aneurysms, 75 (95%) were in the anterior circulation, with a mean diameter of 3.1 mm (range, 2.0–8.0 mm). Subjects with UIAs were significantly older and had more severe hypertension. The carotid flow pulsatility index was significantly lower in subjects with UIAs and negatively and independently correlated with UIAs. Tertile analysis stratified by carotid flow pulsatility index revealed that subjects with lower indices had higher levels of low‐density lipoprotein cholesterol. Conclusions The presence of UIAs correlated with lower carotid flow pulsatility index and elevated low‐density lipoprotein cholesterol in the data from a population of healthy older volunteers. A reduced carotid flow pulsatility index may affect low‐density lipoprotein cholesterol elevation by some molecular pathways and influence the development of cerebral aneurysms. This may guide aneurysm screening indications for institutions where magnetic resonance angiography is not routine.

Item does not contain fulltext IMPORTANCE: Unruptured intracranial aneurysms not undergoing preventive endovascular or neurosurgical treatment are often monitored radiologically to detect aneurysm growth, which is associated with an increase in risk of rupture. However, the absolute risk of aneurysm rupture after detection of growth remains unclear. OBJECTIVE: To determine the absolute risk of rupture of an aneurysm after detection of growth during follow-up and to develop a prediction model for rupture. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data were obtained from 15 international cohorts. Patients 18 years and older who had follow-up imaging for at least 1 untreated unruptured intracranial aneurysm with growth detected at follow-up imaging and with 1 day or longer of follow-up after growth were included. Fusiform or arteriovenous malformation-related aneurysms were excluded. Of the 5166 eligible patients who had follow-up imaging for intracranial aneurysms, 4827 were excluded because no aneurysm growth was detected, and 27 were excluded because they had less than 1 day follow-up after detection of growth. EXPOSURES: All included aneurysms had growth, defined as 1 mm or greater increase in 1 direction at follow-up imaging. MAIN OUTCOMES AND MEASURES: The primary outcome was aneurysm rupture. The absolute risk of rupture was measured with the Kaplan-Meier estimate at 3 time points (6 months, 1 year, and 2 years) after initial growth. Cox proportional hazards regression was used to identify predictors of rupture after growth detection. RESULTS: A total of 312 patients were included (223 [71%] were women; mean [SD] age, 61 [12] years) with 329 aneurysms with growth. During 864 aneurysm-years of follow-up, 25 (7.6%) of these aneurysms ruptured. The absolute risk of rupture after growth was 2.9% (95% CI, 0.9-4.9) at 6 months, 4.3% (95% CI, 1.9-6.7) at 1 year, and 6.0% (95% CI, 2.9-9.1) at 2 years. In multivariable analyses, predictors of rupture were size (7 mm or larger hazard ratio, 3.1; 95% CI, 1.4-7.2), shape (irregular hazard ratio, 2.9; 95% CI, 1.3-6.5), and site (middle cerebral artery hazard ratio, 3.6; 95% CI, 0.8-16.3; anterior cerebral artery, posterior communicating artery, or posterior circulation hazard ratio, 2.8; 95% CI, 0.6-13.0). In the triple-S (size, site, shape) prediction model, the 1-year risk of rupture ranged from 2.1% to 10.6%. CONCLUSION AND RELEVANCE: Within 1 year after growth detection, rupture occurred in approximately 1 of 25 aneurysms. The triple-S risk prediction model can be used to estimate absolute risk of rupture for the initial period after detection of growth.

Casein hydrolysate improves arterial stiffness, as estimated by brachial ankle pulse wave velocity (baPWV), in untreated hypertensive subjects. Facial pigmentation is a useful biomarker for arterial stiffness. This trial evaluated whether casein hydrolysate improves facial pigmentation in association with changes in arterial stiffness. A randomized, double-blind, placebo-controlled trial was conducted in 80 non-hypertensive Japanese participants randomly assigned to receive either active tablets containing casein hydrolysate or placebo for 48 weeks. Facial pigmentation and baPWV were measured at baseline and at the end of the intervention. Other biochemical atherosclerosis-related parameters were also measured, including advanced glycation end products (AGEs). Changes in facial pigmentation showed a significant difference between the groups. Change in baPWV was significantly better in the active than in the placebo group. In contrast, no significant association was seen between changes in facial pigmentation and those in baPWV. Among other atherosclerosis-related factors, changes in advanced glycation products (AGEs) were significantly decreased in the active compared to the placebo group. Further, changes in facial pigmentation were positively correlated with those in AGEs. Changes in AGEs were independently associated with changes in facial pigmentation. Casein hydrolysate improves facial pigmentation in non-hypertensive participants. Casein hydrolysate may have beneficial effects on glycation stress.

Background Magnetic resonance imaging-guided focused ultrasound thalamotomy is approved by the U.S. Food and Drug Administration for treatment of essential tremor. Although this incisionless technology creates an ablative lesion, it potentially avoids serious complications of open stereotactic surgery. Objective To determine the safety profile of magnetic resonance imaging-guided focused ultrasound unilateral thalamotomy for essential tremor, including frequency, and severity of adverse events, including serious adverse events. Methods Analysis of safety data for magnetic resonance imaging-guided focused ultrasound thalamotomy (186 patients, five studies). Results Procedure-related serious adverse events were very infrequent (1.6%), without intracerebral hemorrhages or infections. Adverse events were usually transient and were commonly rated as mild (79%) and rarely severe (1%). As previously reported, abnormalities in sensation and balance were the commonest thalamotomy-related adverse events. Conclusion The overall safety profile of magnetic resonance imaging-guided focused ultrasound thalamotomy supports its role as a new option for patients with medically refractory essential tremor. © 2018 International Parkinson and Movement Disorder Society.

AIM It is well known that consumption of isoflavones reduces the risk of cardiovascular disease. However, the effectiveness of isoflavones in preventing dementia is controversial. A number of intervention studies have produced conflicting results. One possible reason is that the ability to produce equol, a metabolite of a soy isoflavone, differs greatly in individuals. In addition to existing data, we sought to confirm whether an apparent beneficial effect in cognitive function is observed after soy consumption in equol producers compared with non-producers. METHODS The present study was a cross-sectional, observational study of 152 (male/female = 61/91, mean age 69.2 ± 9.2 years) individuals. Participants were divided into two groups according to equol production status, which was determined using urine samples collected after a soy challenge test. Cognitive function was assessed using two computer-based questionnaires (touch panel-type dementia assessment scale [TDAS] and mild cognitive impairment [MCI] screen). RESULTS Overall, 60 (40%) of 152 participants were equol producers. Both TDAS and prevalence of MCI were significantly higher in the equol producer group than in the non-producer group. In univariate analyses, TDAS significantly correlated with age, serum creatinine, estimated glomerular filtration rate and low-density lipoprotein cholesterol. In multiple regression analysis using TDAS as a dependent variable, equol producer (β = 0.236, P = 0.005) was selected as an independent variable. In addition, multiple logistic regression analysis to assess the presence of MCI showed that being an equol producer was an independent risk factor for MCI (odds ratio 3.961). CONCLUSIONS Compared with equol non-producers, equol producers showed an apparent beneficial effect in cognitive function after soy intake. Geriatr Gerontol Int 2017; 17: 2103-2108.

OBJECTIVESkull density ratio (SDR) assesses the transparency of the skull to ultrasound. Magnetic resonance–guided focused ultrasound (MRgFUS) thalamotomy in essential tremor (ET) patients with a lower SDR may be less effective, and the risk for complications may be increased. To address these questions, the authors analyzed clinical outcomes of MRgFUS thalamotomy based on SDRs.METHODSIn 189 patients, 3 outcomes were correlated with SDRs. Efficacy was based on improvement in Clinical Rating Scale for Tremor (CRST) scores 1 year after MRgFUS. Procedural efficiency was determined by the ease of achieving a peak voxel temperature of 54°C. Safety was based on the rate of the most severe procedure-related adverse event. SDRs were categorized at thresholds of 0.45 and 0.40, selected based on published criteria.RESULTSOf 189 patients, 53 (28%) had an SDR < 0.45 and 20 (11%) had an SDR < 0.40. There was no significant difference in improvement in CRST scores between those with an SDR ≥ 0.45 (58% ± 24%), 0.40 ≤ SDR < 0.45 (i.e., SDR ≥ 0.40 but < 0.45) (63% ± 27%), and SDR < 0.40 (49% ± 28%; p = 0.0744). Target temperature was achieved more often in those with an SDR ≥ 0.45 (p < 0.001). Rates of adverse events were lower in the groups with an SDR < 0.45 (p = 0.013), with no severe adverse events in these groups.CONCLUSIONSMRgFUS treatment of ET can be effectively and safely performed in patients with an SDR < 0.45 and an SDR < 0.40, although the procedure is more efficient when SDR ≥ 0.45.

Background Magnetic resonance-guided focused ultrasound thalamotomy (FUS-T) is an emerging treatment for essential tremor (ET). Objective To determine the predictors of outcomes after FUS-T. Methods Two treatment groups were analyzed: 75 ET patients enrolled in the pivotal trial, between 2013 and 2015; and 114 patients enrolled in the postpivotal trials, between 2015 and 2016. All patients had medication-refractory, disabling ET, and underwent unilateral FUS-T. The primary outcome (hand tremor score, 32-point scale with higher scores indicating worse tremor) and the secondary outcome variables (Clinical Rating Scale for Tremor Part C score: 32-point scale with higher scores indicating more disability) were assessed at baseline and 1, 3, 6, and 12 mo. The operative outcome variables (ie, peak temperature, number of sonications) were analyzed. The results between the 2 treatment groups, pivotal and postpivotal, were compared with repeated measures analysis of variance and adjusted for confounding variables. Results A total of 179 patients completed the 12-mo evaluation. The significant predictors of tremor outcomes were patient age, disease duration, peak temperature, and number of sonications. A greater improvement in hand tremor scores was observed in the postpivotal group at all time points, including 12 mo (61.9% ± 24.9% vs 52.1% ± 24.9%, P = .009). In the postpivotal group, higher energy was used, resulting in higher peak temperatures (56.7 ± 2.5 vs 55.6 ± 2.8°C, P = .004). After adjusting for age, years of disease, number of sonications, and maximum temperature, the treatment group was a significant predictor of outcomes (F = 7.9 [1,165], P = .005). Conclusion We observed an improvement in outcomes in the postpivotal group compared to the pivotal group potentially reflecting a learning curve with FUS-T. The other associations of tremor outcomes included patient age, disease duration, peak temperature, and number of sonications.

OBJECTIVES: Dementia, which is characterized by a progressive decline in cognitive function, is a major concern in aging societies. Although a number of treatments have been approved, an effective therapy to prevent the disorder is lacking. A supplement that improves cognitive function would benefit patients. The aim of this study was to assess whether auraptene, a citrus coumarin, has a protective effect on cognitive decline. DESIGN: A randomized, placebo-controlled, double-blind study SETTING: Outpatient medical check-up program for cognitive disorders PARTICIPANTS: 84 adult volunteers (they are cognitively normal) met inclusion and exclusion criteria to participate. INTERVENTION: 42 participants received auraptene enriched (containing 6.0 mg/day of auraptene) test juice, and another participants received placebo juice. MEASUREMENTS: 1) Mild Cognitive Impairment (MCI) Screen using the 10-word immediate recall test. 2) The Mini-Mental State Examination (MMSE). Cognitive assessment ware carried out baseline and at 24 weeks. RESULTS: Auraptene enriched test juice did not improve cognitive function after 24 weeks compared with baseline data. However, there was a significant difference in the percentage change in cognitive function between the test and placebo orange juice groups (6.3 ± 18.9 vs. −2.4 ± 14.8, P < 0.05). Multiple regression analysis demonstrated a significant independent relationship between the percentage change in the 10-word immediate recall test score and test juice consumption including baseline 10-word immediate recall test score in all subjects. CONCLUSION: This is the first study to assess the effectiveness of auraptene in the prevention of cognitive decline. Our results suggest that auraptene is a safe supplement for the prevention of cognitive decline.

We examined whether baPWV could be affected by pork collagen peptide (CP) ingestion. Seventy subjects were randomized into two groups (2.5 g/day CP and 2.5 g/day placebo). A significant reduction in baPWV was observed in the CP group compared to the placebo group. This study demonstrated that pork CP may contribute to the prevention of atherosclerosis in elderly.

Magnetic resonance imaging-guided focused ultrasound thalamotomy is approved by the U.S. Food and Drug Administration for treatment of essential tremor. Although this incisionless technology creates an ablative lesion, it potentially avoids serious complications of open stereotactic surgery.To determine the safety profile of magnetic resonance imaging-guided focused ultrasound unilateral thalamotomy for essential tremor, including frequency, and severity of adverse events, including serious adverse events.Analysis of safety data for magnetic resonance imaging-guided focused ultrasound thalamotomy (186 patients, five studies).Procedure-related serious adverse events were very infrequent (1.6%), without intracerebral hemorrhages or infections. Adverse events were usually transient and were commonly rated as mild (79%) and rarely severe (1%). As previously reported, abnormalities in sensation and balance were the commonest thalamotomy-related adverse events.The overall safety profile of magnetic resonance imaging-guided focused ultrasound thalamotomy supports its role as a new option for patients with medically refractory essential tremor. © 2018 International Parkinson and Movement Disorder Society.

Objective:To develop a risk score that estimates 3-year and 5-year absolute risks for aneurysm growth.Methods:From 10 cohorts of patients with unruptured intracranial aneurysms and follow-up imaging, we pooled individual data on sex, population, age, hypertension, history of subarachnoid hemorrhage, and aneurysm location, size, aspect ratio, and shape but not on smoking during follow-up and family history of intracranial aneurysms in 1,507 patients with 1,909 unruptured intracranial aneurysms and used aneurysm growth as outcome. With aneurysm-based multivariable Cox regression analysis, we determined predictors for aneurysm growth, which were presented as a risk score to calculate 3-year and 5-year risks for aneurysm growth by risk factor status.Results:Aneurysm growth occurred in 257 patients (17%) and 267 aneurysms (14%) during 5,782 patient-years of follow-up. Predictors for aneurysm growth were earlier subarachnoid hemorrhage, location of the aneurysm, age >60 years, population, size of the aneurysm, and shape of the aneurysm (ELAPSS). The 3-year growth risk ranged from 42% and the 5-year growth risk from 60%, depending on the risk factor status.Conclusions:The ELAPSS score consists of 6 easily retrievable predictors and can help physicians in decision making on the need for and timing of follow-up imaging in patients with unruptured intracranial aneurysms.

Accumulation of advanced glycation endproducts (AGEs) is thought to be involved in the pathogenesis of dementia, especially Alzheimer's disease. Tissue AGE accumulation can be estimated using the relative simple noninvasive measurement of skin autofluorescence (SAF), a method based on the fluorescent properties of some AGEs. However, possible involvement of tissue AGE accumulation in mild cognitive impairment (MCI) has not been fully investigated.We investigated whether tissue AGE accumulation estimated by SAF is associated with mild cognitive impairment.We analyzed 226 community-dwelling subjects. In addition to several atherosclerosis-related clinical parameters, MCI screening test, assessment of brain atrophy, and SAF were performed on people aged 40 years. MCI was assessed using the Japanese version of the MCI screening method. Atrophy of the brain was assessed by examining the temporal horn area (THA) by brain MRI.SAF was significantly higher in participants with MCI than in those with normal cognitive function (2.56±0.55 versus 2.10±0.41; p 0.001). Logistic regression analyses with adjustment for confounding factors including age and THA showed that high SAF 2.27 was significantly related to the presence of MCI (odds, 6.402; 95% CI, 1.590-25.773, p = 0.009).We found an association between SAF and MCI, which was independent of brain atrophy, in healthy subjects.

It is well known that consumption of isoflavones reduces the risk of cardiovascular disease. However, the effectiveness of isoflavones in preventing dementia is controversial. A number of intervention studies have produced conflicting results. One possible reason is that the ability to produce equol, a metabolite of a soy isoflavone, differs greatly in individuals. In addition to existing data, we sought to confirm whether an apparent beneficial effect in cognitive function is observed after soy consumption in equol producers compared with non-producers.The present study was a cross-sectional, observational study of 152 (male/female = 61/91, mean age 69.2 ± 9.2 years) individuals. Participants were divided into two groups according to equol production status, which was determined using urine samples collected after a soy challenge test. Cognitive function was assessed using two computer-based questionnaires (touch panel-type dementia assessment scale [TDAS] and mild cognitive impairment [MCI] screen).Overall, 60 (40%) of 152 participants were equol producers. Both TDAS and prevalence of MCI were significantly higher in the equol producer group than in the non-producer group. In univariate analyses, TDAS significantly correlated with age, serum creatinine, estimated glomerular filtration rate and low-density lipoprotein cholesterol. In multiple regression analysis using TDAS as a dependent variable, equol producer (β = 0.236, P = 0.005) was selected as an independent variable. In addition, multiple logistic regression analysis to assess the presence of MCI showed that being an equol producer was an independent risk factor for MCI (odds ratio 3.961).Compared with equol non-producers, equol producers showed an apparent beneficial effect in cognitive function after soy intake. Geriatr Gerontol Int 2017; 17: 2103-2108.

Background: Given the very poor outcome of ruptured intracranial aneurysms, detection and treatment of unruptured intracranial aneurysms by a less invasive examination have become important. For this purpose, 3-tesla (3T) magnetic resonance imaging (MRI) is the most suitable candidate, owing to its high signal/noise ratio and frequency resolution. However, few reports have investigated the prevalence of intracranial aneurysms with high-tesla MRI. Here, we evaluated the prevalence of intracranial aneurysms and the effectiveness of a 3T MRI system in their detection. Methods: During a 1-year period, a total of 3,414 consecutive patients undergoing MR angiography with 3T MRI for the first time were enrolled. Diagnosis of intracranial aneurysm was made by two neuroradiologically trained medical doctors under complete blinding to patient information. When intracranial aneurysm was suspected, volume-rendering images were created for more accurate diagnosis. Results: Surprisingly, 317 unruptured intracranial aneurysms were identified in 286 of 3,414 cases (8.4%); 151 unruptured aneurysms (47.6%) occurred in the internal carotid artery, 85 (26.8%) in the middle cerebral artery, 54 (17.0%) in the anterior cerebral artery, and 27 (8.5%) in the posterior circulation. Of these, 152/317 (47.9%) were 7 mm. No significant difference in size was seen among the four locations.Conclusions: For the first time, this study assessed the detection rate of intracranial aneurysms using 3T MRI. Results showed a higher detection rate than previously documented. The reason for this higher rate is likely the improved ability of this modality to detect unruptured aneurysms in the internal carotid artery and those

CASとCEAの周術期および長期成績を明らかにするため，急性期手術，慢性期手術に分けて検討した．対象は1998年1月から2006年10月までに当院で頚部内頚動脈血行再建術を施行された連続103症例（CAS 52例，CEA 51例）とした．周術期成績：慢性期手術の成績は，CAS, CEAともに永続的神経障害2.1%，死亡例0例と良好であった．これに対し急性期手術の成績は，死亡例は0例であったが，永続的神経障害はCAS, CEAとも25%と高率であった．長期成績：脳梗塞発症は，急性期手術・慢性期手術ともにCASでは平均追跡期間3年，CEAでは平均追跡期間4年3カ月の間認めなかった．ADLを低下させた他疾患の発症は，慢性期手術ではCASで7.9%，CEAで19%であり，急性期手術ではCAS, CEAともに0%であった．CASは長期成績も良好であり，CEA high risk症例に対する治療として期待がかかる．

In acute stroke, the target of therapy is the severely hypoxic but salvageable tissue. Previous human studies using 18F-fluoromisonidazole and positron emission tomography (18F-FMISO PET) have shown high tracer retention indicative of tissue hypoxia, which had normalized at repeat scan >48 h later. In the only validation study of 18F-FMISO, using ex vivo autoradiography in thread middle cerebral artery occluded (MCAo) rats, there was unexpected high uptake as late as 22 h after reperfusion, raising questions about the use of 18F-FMISO as a hypoxia tracer. Here we report a pilot study of 18F-FMISO PET in experimental stroke. Spontaneous hypertensive rats were subjected to distal clip MCAo. Three-hour dynamic PET was performed in 7 rats: 3 normals, 1 with permanent MCAo (two sessions: 30 mins and 48 h after clip), and 3 with temporary MCAo (45 mins, n = 1; 120 mins, n = 2; scanning started 30 mins after clip removal). Experiments were terminated by perfusion—fixation for standard histopathology. Late tracer retention was assessed by both compartmental modelling and simple side-to-side ratios. In the initial PET session of the permanent MCAo rat, striking trapping of 18F-FMISO was observed in the affected cortex, which had normalized 48 h later; histopathology revealed pannecrosis. In contrast, there was no demonstrable tracer retention in either temporary MCAo models, and histopathology showed ischemic changes only. These results document elevated 18F-FMISO uptake in the stroke area only in the early phase of MCAo, but not after early reperfusion nor when tissue necrosis has developed. These findings strongly support the validity of 18F-FMISO as a marker of viable hypoxic tissue/penumbra after stroke.

We reported the dural AVF case with sinus stenosis, that was entirely treated through the stenting procedure. 61-year-old male had been realizing the attack which causes bilateral visual problem. He would have suffered from the intracranial hypertension caused by dural AVF in the right transverse sinus and left transverse sinus stenosis. We performed TVE and sinus stenting, then used the antiplatelet and the anticoagulant. However, six months later, he suffered from SAH due to recurrence of dural AVF. We performed TVE again, denser packing than usual. Two years later, he have no symptom, angiographically, there was no recurrence of dural AVF and patency of stented sinus. We think denser embolizations should have performed in case of dural AVF with sinus stenting.

We evaluated neuropsychological function, magnetic resonance (MR) images and cerebral blood flow (CBF) in patients with unruptured asymptomatic cerebral aneurysms. Among consecutive operations (n=73) on 70 patients since 2000, direct surgery was performed in 53 operations on 50 patients, and intravascular surgery was performed in 20 operations on 20 patients. Surgical results of direct surgery were studied. Direct surgery was selected mainly for patients with small and anterior circulation aneurysms. MR imaging was conducted 1 week after surgery, and Wechsler Adult Intelligence Scale-Revised (WAIS-R) examination and CBF measurement using 133Xe-SPECT were done before and 1 month after surgery. Abnormal neurological findings were recognized postoperatively in 26% of surgeries. Among them, visual disturbance was permanent in 4% of surgeries, all of which were surgeries for paraclinoid internal carotid artery aneurysms. WAIS-R results deteriorated in 26% of surgeries at 1 month and at least in 5% of surgeries at 1 year after surgery. MR images at 1 week after surgery revealed brain damage in 30% of surgeries and subdural fluid collection in 19% of surgeries. Patients with large brain damage or thick subdural fluid collection frequently showed neurological deficits and/or WAIS-R deterioration. These complications were recognized frequently in patients with ACoA aneurysms. Resting CBF decreased significantly in the area supplied by the anterior cerebral artery and anterior border zone on the operated side postoperatively. The brain damage and subdural fluid collection were observed frequently and caused neurological deficits and neuropsychological dysfunction, although these were usually transient. It may be necessary to evaluate neuropsychological function, MRI and CBF in patients with unruptured asymptomatic cerebral aneurysms to improve surgical results.

Purpose Although time-of-flight (TOF)-magnetic resonance angiography (MRA) can clearly depict intracranial arteries, the arterial flow of middle cerebral artery (MCA) is occasionally not detected. We evaluated this phenomenon with reference to cerebrovascular dynamics. Materials and Methods Seventeen patients with suspected occlusion of MCA or internal carotid artery on TOF-MRA were enrolled. All patients underwent CT angiography (CTA) and quantitative cerebral blood flow (CBF) examination for measurement of resting CBF and cerebrovascular reactivity (CVR). Depending on appearance, patients were categorized into three groups. Group A (n=6) had MCA delineation on both MRA and CTA, while groups B (n=6) and C (n=5) had no signal on MRA, but Group B had a MCA delineation on CTA. Results No significant difference between resting CBF and CBF after the administration of acetazolamide was seen among 3 groups. In contrast, mean CVR in group B was -19.7±18.1%, which was significantly lower than group A [36.4±21.7% (p

Background We evaluated the utility of 3-dimensional (3-D) ultrasound imaging for assessment of carotid artery stenosis, as compared with similar assessment via magnetic resonance angiography (MRA). Methods Subjects comprised 58 patients with carotid stenosis who underwent both 3-D ultrasound imaging and MRA. We studied whether abnormal findings detected by ultrasound imaging could be diagnosed using MRA. Ultrasound images were generated using Voluson 730 Expert and Voluson E8. Results The degree of stenosis was mild in 17, moderate in 16, and severe in 25 patients, according to ultrasound imaging. Stenosis could not be recognized using MRA in 4 of 17 patients diagnosed with mild stenosis using ultrasound imaging. Ultrasound imaging showed ulceration in 13 patients and mobile plaque in 6 patients. When assessing these patients, MRA showed ulceration in only 2 of 13 patients and did not detect mobile plaque in any of these 6 patients. Static 3-D B mode images demonstrated distributions of plaque, ulceration, and mobile plaque, and static 3-D flow images showed flow configuration as a total structure. Real-time 3-D B mode images demonstrated plaque and vessel movement. Carotid artery stenting was not selected for patients diagnosed with ulceration or mobile plaque. Conclusions Ultrasound imaging was necessary to detect mild stenosis, ulcerated plaque, or mobile plaque in comparison with MRA, and 3-D ultrasound imaging was useful to recognize carotid stenosis and flow pattern as a total structure by static and real-time 3-D demonstration. This information may contribute to surgical planning.

It was previously reported that prosaposin possesses neurotrophic activity that is ascribed to an 18-mer peptide comprising the hydrophilic sequence of the rat saposin C domain. To evaluate the effect of the 18-mer peptide on ischemic neuronal damage, the peptide was infused in the left lateral ventricle immediately after occlusion of the left middle cerebral artery (MCA) in stroke-prone spontaneously hypertensive (SP-SH) rats. The treatment ameliorated the ischemia-induced space navigation disability and cortical infarction and prevented secondary thalamic degeneration in a dose-dependent manner. In culture experiments, treatment with the 18-mer peptide attenuated free radical-induced neuronal injury at low concentrations (0.002 to 2 pg/mL), and the peptide at higher concentrations (0.2 to 20 ng/mL) protected neurons against hypoxic insult. Furthermore, a saposin C fragment comprising the 18-mer peptide bound to synaptosomal fractions of the cerebral cortex, and this binding decreased at the 1st day after MCA occlusion and recovered to the preischemic level at the 7th day after ischemia. These findings suggest that the 18-mer peptide ameliorates neuronal damage in vivo and in vitro through binding to the functional receptor, although the cDNA encoding prosaposin receptor has not been determined yet.

Erythropoietin (EPO) prevents the ischemia-induced delayed neuronal death in the hippocampal CA1 field in gerbils. EPO receptor (EPOR) is also expressed in the cerebral cortex but its function is not known. To examine whether EPO has a neuroprotective action in the cortex, EPO was infused into the cerebroventricles of stroke-prone spontaneously hypertensive rats with permanent occlusion of the left middle cerebral artery. Morris water maze test indicated that EPO infusion alleviated the ischemia-induced place navigation disability. The left (ischemic)-to-right (contralateral nonischemic) (L/R) ratio of cerebrocortical area in the EPO-infused ischemic group was larger than that in the vehicle-infused ischemic group. The occlusion caused secondary thalamic degeneration but infusion of EPO prevented the decrease in the L/R ratio of thalamic area and supported neuron survival in the ventroposterior thalamic nucleus. In situ hybridization indicated that EPOR mRNA was upregulated in the periphery (ischemic penumbra) of a cerebrocortical infarct after occlusion of the middle cerebral artery, suggesting that an increased number of EPOR in neurons facilitates the EPO signal transmission, thereby preventing the damaged area from enlarging.

Background: Although rupture of unruptured intracranial aneurysms (UIAs) is closely associated with UIA growth during follow-up, few studies have investigated how UIAs grow during observation. Hypertension appears to affect the formation of intracranial aneurysms. However, few studies have investigated the association of blood pressure variability with UIA growth. Visit-to-visit variability (VVV) in systolic blood pressure (SBP) is a newly defined concept which appears to be a good predictor of stroke. With this factor in mind, here we conducted a prospective analysis of the results of 2 years of observation of UIAs by magnetic resonance angiography (MRA) and sought to identify risk factors for UIA growth and rupture. Methods: From December 2006 through June 2010, two hundred patients with 212 UIAs were followed for 2 years. Patient ages ranged from 31 to 91 years. Putative risk factors for the growth of UIAs were evaluated. Subjects were divided into two groups: a UIA growth group consisting of patients whose UIAs increased by 1 mm or more in size or who developed subarachnoid hemorrhage (SAH), and an unchanged group. Brachial blood pressure values were recorded at the time of diagnosis and during follow-up in the outpatient clinic. All blood pressure values were then averaged, and the VVV of SBP was defined as the standard deviation (SD) of a minimum of 5 blood pressure measurements at outpatient visits. Results: UIA growth occurred in 20 patients and SAH occurred in 1 patient. Current smoking tended to be more prevalent in the UIA growth group (p < 0.01). Five of the 12 patients with multiple UIAs showed UIA growth within 2 years and multiplicity was a significant risk factor for UIA growth (p < 0.01). The mean baseline size in the UIA growth group was larger than that in the unchanged group (p = 0.01) and 7 of the 18 patients with large UIAs, categorized as having an initial diameter of 7 mm or more, had an increase in UIA size over the 2 years (p < 0.01). On multivariable logistic regression analysis, current smoking, multiplicity, and UIA size ≥7 mm were significant risk factors for UIA growth. Although no significant difference was seen between the UIA growth and unchanged groups in office SBP during the observation period, VVV in SBP was significantly higher in the UIA growth group than in the unchanged group, and it was significantly and independently associated with UIA growth. Conclusions: VVV in SBP is a novel risk factor for the growth of UIAs and may be a key factor for the prevention of UIA rupture. Future research is needed to confirm that SBP stability prevents UIA rupture.

Background Cerebral microbleeds (CMBs) detected on T2*-weighted MRI gradient-echo have been associated with increased risk of cerebral infarction. We evaluated risk factors for these lesions in a cohort of first-time ischemic stroke patients. Methods Presence of CMBs in consecutive first-time ischemic stroke patients was evaluated. The location of CMBs was classified by cerebral region as strictly lobar (lobar CMBs) and deep or infratentorial (deep CMBs). Logistic regression analysis was performed to determine the contribution of lipid profile to the presence of CMBs. Results One hundred and sixteen patients with a mean age of 70 ± 10 years were recruited. CMBs were present in 74 patients. The deep CMBs group had significantly lower HDL-C levels than those without CMBs. In univariable analysis, advanced periventricular hyperintensity grade (PVH > 2) and decreased HDL-C were significantly associated with the deep but not the lobar CMB group. On logistic regression analysis, HDL-C (beta = − 0.06, p = 0.002) and PVH grade > 2 (beta = 3.40, p = 0.005) were independent determinants of deep CMBs. Conclusions Low HDL-C may be a risk factor of deep CMBs, including advanced PVH status, in elderly patients with acute ischemic stroke. Management of HDL-C levels might be a therapeutic target for the prevention of recurrence of stroke.

Purpose: Aspirin is protective against ischemic stroke, but its use is a significant risk factor for gastro-esophageal reflux disease (GERD). We investigated the prevalence and associated clinical factors of GERD in ischemic stroke patients treated with aspirin. Methods: We recruited 116 ischemic stroke outpatients who were receiving aspirin. Sixteen patients who had received proton pump inhibitors or H2 receptor antagonists within the previous month were excluded. The presence of GERD was defined using the GerdQ questionnaire, with a score of 8 or higher considered positive for GERD. Logistic regression analysis was conducted using variables which exhibited a significant correlation coefficient on two-group comparison as factors, with the presence or absence of GERD as the dependent variable. Results: Mean age of the 100 patients analyzed was 69.3 ± 8.9 years. The prevalence of GERD was 28%. Mean BW of patients with GERD was significantly higher than of those without GERD (P =0.02). The proportion of patients receiving angiotensin II receptor blockers (ARBs) was significantly lower in the GERD group (P=0.04). In contrast, no significant difference was seen in the proportion of patients receiving calcium channel blockers (CCBs). Multivariable logistic regression analysis showed that ARB disuse and increased BW were independent predictors of GERD. Conclusions: The prevalence of GERD was 28% in ischemic stroke patients treated with aspirin. Increased BW as well as ARBs disuse was independent risk factors of GERD. With all these factors, ARBs appear to be better suited than CCBs for use in patients with ischemic stroke with regard to the prevention of GERD. A comprehensive understanding of the relationship between ARBs and GERD prevalence awaits additional studies in a larger number of patients.

Background: Cerebral microbleed (CMB), which is conspicuous on gradient-echo T2*-weighted magnetic resonance imaging, is a risk factor of intracerebral hemorrhage (ICH). CMBs have been detected even in neurologically healthy persons, who also seem prone to be affected by stroke, not only ICH but also cerebral infarction. Methods and Results: The presence of CMB was investigated in brain dock participants, making reference to silent lacunar infarction (SLI). Participants comprised 377 neurologically healthy persons and 21 (5.6%) had CMB detected, which was associated with a high incidence of hypertension, other conventional risk factors having no significant correlation with CMB. In a simple correlation analysis, CMB showed a positive association with age and systolic blood pressure (SBP). Logistic regression analysis revealed that SLI was the factor most strongly associated with CMB. Moreover, individuals who had both CMB and SLI had higher SBP than other groups. Conclusions: The etiology of CMB is similar to that of SLI. (Circ J 2009; 73: 530 - 533)

The thalamus degenerates following cerebral infarction in the territory supplied by the middle cerebral artery (MCA), and apoptosis is suspected to be the mechanism of this phenomenon. The author studied the role of the growth arrest and DNA damage-inducible gene (GADD) 153 in this thalamic degeneration. The MCA was occluded in stroke-prone spontaneously hypertensive rats. The expression of GADD 153 and Bcl-2, and the release of cytochrome c from the mitochondria to cytosol, were examined in the thalamus until 7 days after ischemia using in situ hybridization, immunoblot, immunohistochemistry and RT-PCR analyses. Gadd153 mRNA expression and GADD153 protein increased transiently at 2, 3, 5 and 7 days, and at 3 and 5 days after ischemia. Bcl-2 mRNA expression and Bcl-2 protein decreased at 3 and 5 days. The release of cytochrome c from the mitochondria was detected at 5 days. These results suggest that increased GADD 153 suppresses Bcl-2 expression, which causes the release of cytochrome c from the mitochondria and leads to thalamic degeneration.

Dynamic MR imaging provides hemodynamic information about normal and pathologic tissue of the brain. The purpose of our study was to evaluate the usefulness of dynamic MR imaging in the assessment of tumor vascularity and the tumor tissue blood flow of meningiomas. We studied 13 patients with meningiomas using dynamic spin-echo MR imaging. The histological subtypes of meningioma were confirmed by the examination of surgical specimens in all patients, and tumors were meningothelial in 9 cases, fibrous in 2, transitional in 1, and psammomatous in 1. Serial images were obtained every 18-24 sec for 8 minutes and 30 seconds after rapid injection of gadolinium diethylenetriaminepentaacetic acid. Different parameters (time to peak, maximum of signal intensity and the washout ratio) were calculated directly from signal intensity curves. As an indicator of tumor vascularity, microvessel density was counted based on immunohistochemically stained sections and tumor tissue blood flow was measured using an xenon-CT system. The maximum of signal intensity corresponded to the tumor vascularity. With dynamic MR imaging, the time intensity curves (TI curves) were divided into two patterns; type 1 had a steep increase with a peak and type 2 had a slow increase to a peak followed by plateau. The maximum of signal intensity measured from TI curve of dynamic MR imaging correlated significantly with microvessel density (R2 = 0.840, p0.0001). Linear regression revealed a significant positive relation between the washout ratio and the tumor tissue blood flow in group showed type 1 on TI curve (R2 = 0.961, p0.001). There was also a significant negative correlation between the time to peak and the tumor tissue blood flow (R2 = 0.792, p0.01). We suggest that dynamic MR imaging is useful for evaluating hemodynamics of meningiomas.

The effect of platelet factor 4 (PF4) on myoblast cultures with or without basic fibroblast growth factor (bFGF) or other growth factors was investigated in the present in vitro experiments, with reference to bFGF binding to myoblast membrane fraction. When PF4 was added to the culture medium 1 day after myoblast cultivation, the nuclei of both myoblasts and myotubes were markedly reduced in number in a dose-dependent manner, whereas the inhibitory effect of PF4 on myoblast development was not observed when PF4 was added to the culture medium 3, 7, or 14 days after myoblast cultivation. In contrast, bFGF significantly increased the numbers of myoblast and myotube nuclei. When bFGF and PF4 were simultaneously added to the culture medium, PF4 abolished the facilitatory effects of bFGF on myogenesis. The real-time biospecific interaction analysis (BIA) core system showed that the myoblast membrane fraction at 1 day after cultivation contains bFGF-binding elements which are blocked by PF4 in a dose-dependent manner. Moreover, [125I]-bFGF binding experiments indicated the existence of both high and low affinity binding sites on myoblast membranes, although the high affinity binding sites decreased in number and the dissociation constant increased in value as the culture period was prolonged. Among the six other growth factors examined, acidic fibroblast growth factor and platelet-derived growth factor-BB stimulated myogenesis, and their effects were blocked by PF4 treatment. These findings suggest that: 1) PF4 inhibits myoblast proliferation and myotube formation only for a limited initial period of cultivation, possibly because of the time-dependent down-regulation of high affinity bFGF receptors: and 2) PF4 may be used as a tool to investigate the function of endogenous heparin-binding growth factors upregulated transiently at a certain developmental stage or in case of tissue damage and repair, even though it is not monospecific to bFGF.

Preoperative thallium-201 (201Tl) single photon emission computed tomography (SPECT) was used to evaluate the histological malignancy in 24 patients with brain tumors. A corrected L/E ratio was calculated based on the ratio of thallium uptake in the tumor on early images versus the tumor in the delayed images (L/E ratio) corrected for thallium uptake in the contralateral cerebral hemisphere. The corrected L/E ratio in benign brain tumors was 0.79 ± 0.23, significantly different to 1.32 ± 0.25 in high grade astrocytomas (p < 0.01) and 1.19 ± 0.05 in metastatic brain tumors (p < 0.01), respectively. The corrected L/E ratio in low grade astrocytomas was 0.64 ± 0.32, significantly lower than that in high grade astrocytomas (p < 0.01) and metastatic brain tumors (p < 0.05). There was one false positive result among 24 patients using a threshold of 1.0 to separate malignant and benign tumors. 201Tl SPECT using the corrected L/E ratio is effective for determining the malignant viability of tumors.

Interleukin-6 (IL-6) has been shown to have potent neurotrophic activity on peripheral and central neurons in vitro. However, it remains to be determined whether or not IL-6 rescues hippocampal CA1 neurons from lethal ischemia and prevents ischemia-induced learning disability. In the present in vivo study, we infused IL-6 continuously for 7 days into the lateral ventricle of gerbil starting 2 h before 3-min forebrain ischemia. IL-6 infusion prevented the occurrence of ischemia-induced learning disability in a dose-dependent manner as revealed by a step-down passive avoidance task. Subsequent light and electron microscopic examinations showed that pyramidal neurons in the CA1 region of the hippocampus as well as synapses within the strata moleculare, radiatum and oriens of the region were significantly more numerous in gerbils infused with IL-6 than in those receiving vehicle infusion. These findings suggest that IL-6 has a trophic effect on ischemic hippocampal neurons.