BACKGROUND: Atrial fibrillation (AF) is a strong risk factor for Alzheimer's disease (AD) independent of ischemic stroke. However, the clinicopathological impact of AF on the severity of AD has not been well elucidated. We aimed to investigate the clinical differences between dementia patients with AF and those without AF by means of imaging data. METHODS: Following approval from the institutional ethics committee, patients with newly diagnosed AD or amnestic mild cognitive impairment (aMCI) were retrospectively screened (n = 170, 79.5 ± 7.4 years old). Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Based on the MRI data, the cerebral volume, cerebral microbleeds (CMBs), periventricular white matter lesions (WMLs), and deep WMLs were evaluated. The regional cerebral blood flow (rCBF) was measured using 123I-IMP SPECT. RESULTS: Of the patients, 14 (8.2%) and 156 (91.8%) had AF (AF group) and sinus rhythm (SR group), respectively. The AF group had significantly lower MMSE scores than the SR group (average [standard deviation (SD)]: 19.4 [4.4] and 22.0 [4.4], respectively; p = 0.0347). Cerebral volume and CMBs did not differ between the two groups. The periventricular WMLs, but not the deep WMLs, were significantly larger in the AF group than in the SR group (mean [SD] mL: 6.85 [3.78] and 4.37 [3.21], respectively; p = 0.0070). However, there was no significant difference in rCBF in the areas related to AD pathology between the two groups. CONCLUSION: AD and aMCI patients with AF showed worse cognitive decline along with larger periventricular WMLs compared to those with SR, although the reduction of rCBF was not different between patients with AF and SR. The white matter lesions may be a more important pathology than the impairment of cerebral blood flow in dementia patients with AF. A larger study is needed to confirm our findings in the future.

INTRODUCTION: Present study was to investigate hs-CRP concentration, brain structural alterations, and cognitive function in the context of AD [Subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD]. METHODS: We retrospectively included 313 patients (Mean age = 76.40 years, 59 SCD, 101 MCI, 153 AD) in a cross-sectional analysis and 91 patients (Mean age = 75.83 years, 12 SCD, 43 MCI, 36 AD) in a longitudinal analysis. Multivariable linear regression was conducted to investigate the relationship between hs-CRP concentration and brain structural alterations, and cognitive function, respectively. RESULTS: Hs-CRP was positively associated with gray matter volume in the left fusiform (β = 0.16, pFDR = 0.023) and the left parahippocampal gyrus (β = 0.16, pFDR = 0.029). Post hoc analysis revealed that these associations were mainly driven by patients with MCI and AD. The interaction of diagnosis and CRP was significantly associated with annual cognitive changes (β = 0.43, p = 0.008). Among these patients with AD, lower baseline CRP was correlated with greater future cognitive decline (r = -0.41, p = 0.013). CONCLUSION: Our study suggests that increased hs-CRP level may exert protective effect on brain structure alterations and future cognitive changes among patients already with cognitive impairment.

BACKGROUND AND PURPOSE: Ginkgo biloba extract (GBE) reportedly ameliorates cognitive function in patients with chronic cerebrovascular insufficiency. However, its efficacy in healthy adults is ambiguous. It was reported that concentrations of terpene lactones, active components of GBE that are present in very low concentrations in the brain, were significantly increased following administration of a mixture of GBE, sesame seed, and turmeric (GBE/MST) in mice. This study aims to investigate the effectiveness of GBE/MST on the cognitive function of healthy adults by comparing it with that of GBE alone. METHODS: Altogether, 159 participants providing informed consent will be recruited from a population of healthy adults aged 20-64 years. Normal cognitive function at baseline will be confirmed using the Japanese version of the Montreal Cognitive Assessment battery. Participants will be randomly assigned in a double-blind manner to the GBE/MST, GBE, and placebo groups in a 1:1:1 ratio. The Wechsler Memory Scale, Trail Making Test, and Stroop Color and Word Test will be used to assess the memory and executive functions at baseline and at the endpoint (24 weeks). For biological assessment, resting state functional magnetic resonance imaging (rs-fMRI) will be performed simultaneously with the neuropsychological tests. DISCUSSION: This study aims to obtain data that can help compare the profile changes in memory and executive functions among participants consuming GBE/MST, GBE alone, and placebo for 24 weeks. Alterations in the default mode network will be evaluated by comparing the rs-fMRI findings between baseline and 24 weeks in the aforementioned groups. Our results may clarify the impact of GBE on cognitive function and the functional mechanism behind altered cognitive function induced by GBE components. TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; registration number: UMIN000043494). This information can be searched on the website of the International Clinical Trials Registry Platform Search Portal of the World Health Organization under the Japan Primary Registries Network.

BACKGROUND AND PURPOSE: In terms of the gut-brain axis, constipation has been considered to be an important factor of neurodegenerative diseases, although the exact mechanism is still controversial. Herein, we aimed to investigate the contribution of constipation to the progression of dementia in a retrospective study. METHODS: Patients of Alzheimer's disease(AD) and amnestic mild cognitive impairment were consecutively screened between January 2015 and December 2020, and those of whom brain MRI and neuropsychological tests were performed twice were enrolled in this study. Participants were classified into with constipation (Cons[+], n = 20) and without constipation (Cons[-], n = 64) groups. Laboratory data at the first visit were used. Regression analysis was performed in MMSE, ADAS-Cog, and the volumes of hippocampus on MRI-MPRAGE images and deep white matter lesions (DWMLs) on MRI-FLAIR images obtained at two different time points. RESULTS: The main finding was that the Cons[+] group showed 2.7 times faster decline in cognitive impairment compared with the Cons[-] group, that is, the liner coefficients of ADAS-Cog were 2.3544 points/year in the Cons[+] and 0.8592 points/year in the Cons[-] groups. Ancillary, changes of DWMLs showed significant correlation with the time span (p < 0.01), and the liner coefficients of DWMLs were 24.48 ml/year in the Cons[+] and 14.83 ml/year in the Cons[-] group, although annual rate of hippocampal atrophy was not different between the two groups. Moreover, serum homocysteine level at baseline was significantly higher in the Cons[+] group than Cons[-] group (14.6 ± 6.4 and 11.5 ± 4.2 nmol/ml, respectively: p = 0.03). CONCLUSION: There is a significant correlation between constipation and faster progression of AD symptoms along with expansion of DWMLs.

Atrial fibrillation (AF) predisposes patients to develop cognitive decline and dementia. Clinical and epidemiological data propose that catheter ablation may provide further benefit to improve neurocognitive function in patients with AF, but the underlying mechanism is poorly available. Here, we conducted a pilot prospective study to investigate whether AF ablation can alter regional cerebral blood flow (rCBF) and brain microstructures, using multimodal magnetic resonance imaging (MRI) technique. Eight patients (63 ± 7 years) with persistent AF underwent arterial-spin labeling (ASL) perfusion, 3D T1-structural images and cognitive test batteries before and 6 months after intervention. ASL and structural MR images were spatially normalized, and the rCBF and cortical thickness of different brain areas were compared between pre- and 6-month post-treatment. Cognitive-psychological function was improved, and rCBF was significantly increased in the left posterior cingulate cortex (PCC) (p = 0.013), whereas decreased cortical thickness was found in the left posterior insular cortex (p = 0.023). Given that the PCC is a strategic site in the limbic system, while the insular cortex is known to play an important part in the central autonomic nervous system, our findings extend the hypothesis that autonomic system alterations are an important mechanism explaining the positive effect of AF ablation on cognitive function.

Both objective and perceived social isolations were associated with future cognitive decline and increase risk of Alzheimer's disease (AD). However, the impacts of perceived social isolation depending on different clinical stages of AD have not been elucidated. The aim of this study was to investigate the influence of perceived social isolation or loneliness on brain structure and future cognitive trajectories in patients who are living with or are at risk for AD. A total of 176 elderly patients (mean age of 78 years) who had complaint of memory problems (39 subjective cognitive decline [SCD], 53 mild cognitive impairment [MCI], 84 AD) underwent structural MRI and neuropsychological testing. Loneliness was measured by one binary item question "Do you often feel lonely?." Voxel-based morphometry was conducted to evaluate regional gray matter volume (rGMV) difference associated with loneliness in each group. To evaluate individual differences in cognitive trajectories based on loneliness, subgroup analysis was performed in 51 patients with AD (n = 23) and pre-dementia status (SCD-MCI, n = 28) using the longitudinal scores of Alzheimer's Disease Assessment Scale-cognitive component-Japanese version (ADAS-Jcog). Whole brain VBM analysis comparing lonely to non-lonely patients revealed loneliness was associated with decreased rGMV in bilateral thalamus in SCD patients and in the left middle occipital gyrus and the cerebellar vermal lobules I - V in MCI patients. Annual change of ADAS-Jcog in patients who reported loneliness was significantly greater comparing to these non-lonely in SCD-MCI group, but not in AD group. Our results indicate that perceived social isolation, or loneliness, might be a comorbid symptom of patients with SCD or MCI, which makes them more vulnerable to the neuropathology of future AD progression.

Recently, type 2 diabetes mellitus (T2DM) has been reported to be strongly associated with Alzheimer's disease (AD). This is partly due to insulin resistance in the brain. Insulin signaling and the number of insulin receptors may decline in the brain of T2DM patients, resulting in impaired synaptic formation, neuronal plasticity, and mitochondrial metabolism. In AD patients, hypometabolism of glucose in the brain is observed before the onset of symptoms. Amyloid-β accumulation, a main pathology of AD, also relates to impaired insulin action and glucose metabolism, although ketone metabolism is not affected. Therefore, the shift from glucose metabolism to ketone metabolism may be a reasonable pathway for neuronal protection. To promote ketone metabolism, medium-chain triglyceride (MCT) oil and a ketogenic diet could be introduced as an alternative source of energy in the brain of AD patients.

BACKGROUND AND AIM: We determined to investigate the incidence and clinical impact of new cerebral microbleeds after intravenous thrombolysis in patients with acute stroke. METHODS: The THAWS was a multicenter, randomized trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with wake-up stroke or unknown onset stroke. Prescheduled T2*-weighted imaging assessed cerebral microbleeds at three time points: baseline, 22-36 h, and 7-14 days. Outcomes included new cerebral microbleeds development, modified Rankin Scale (mRS) ≥3 at 90 days, and change in the National Institutes of Health Stroke Scale (NIHSS) score from 24 h to 7 days. RESULTS: Of all 131 patients randomized in the THAWS trial, 113 patients (mean 74.3 ± 12.6 years, 50 female, 62 allocated to intravenous thrombolysis) were available for analysis. Overall, 46 (41%) had baseline cerebral microbleeds (15 strictly lobar cerebral microbleeds, 14 mixed cerebral microbleeds, and 17 deep cerebral microbleeds). New cerebral microbleeds only emerged in the intravenous thrombolysis group (seven patients, 11%) within a median of 28.3 h, and did not additionally increase within a median of 7.35 days. In adjusted models, number of cerebral microbleeds (relative risk (RR) 1.30, 95% confidence interval (CI): 1.17-1.44), mixed distribution (RR 19.2, 95% CI: 3.94-93.7), and cerebral microbleeds burden ≥5 (RR 44.9, 95% CI: 5.78-349.8) were associated with new cerebral microbleeds. New cerebral microbleeds were associated with an increase in NIHSS score (p = 0.023). Treatment with alteplase in patients with baseline ≥5 cerebral microbleeds resulted in a numerical shift toward worse outcomes on ordinal mRS (median [IQR]; 4 [3-4] vs. 0 [0-3]), compared with those with <5 cerebral microbleeds (common odds ratio 17.1, 95% CI: 0.76-382.8). The association of baseline ≥5 cerebral microbleeds with ordinal mRS score differed according to the treatment group (p interaction = 0.042). CONCLUSION: New cerebral microbleeds developed within 36 h in 11% of the patients after intravenous thrombolysis, and they were significantly associated with mixed-distribution and ≥5 cerebral microbleeds. New cerebral microbleeds development might impede neurological improvement. Furthermore, cerebral microbleeds burden might affect the effect of alteplase.

AIMS: We have previously reported 5-year follow-up data on the TIAregistry.org, an international prospective cohort in patients with transient ischemic attack (TIA) or minor stroke. We conducted a Japanese subgroup analysis because outcomes and predictors might differ according to ethnicities and regions. In this study, we compared the baseline and 5-year follow-up data of Japanese and non-Japanese patients with TIA or minor stroke. METHODS: Patients with TIA or minor ischemic stroke within 7 days after the onset were classified into two groups based on ethnicity, Japanese (n=345) and non-Japanese (n=3502); further, 5-year event rates were compared between the two groups. We also determined predictors of 5-year stroke for both groups. RESULTS: Vascular death and death from any cause were identified to be less prevalent, unlike stroke and intracranial hemorrhage, which was determined to be more prevalent in Japanese than in non-Japanese patients. Five-year rate of stroke was significantly higher in Japanese patients. Cumulative stroke and major cardiovascular event rates did not decline but instead linearly increased from 1 to 5 years in both groups. Baseline risk factors for 5-year stroke were as follows: age, diabetes, history of stroke or TIA, and congestive heart failure in Japanese patients. Independent predictors of 5-year stroke were large artery atherosclerosis, congestive heart failure, diabetes, and age in Japanese patients. CONCLUSIONS: Recurrent stroke and intracranial hemorrhage were determined to be more prevalent at 5 years after TIA or minor stroke in Japanese patients than in non-Japanese patients. Strategies to mitigate the long-term risks of stroke, aside from adherence to current guidelines, should take Japanese-patient-specific residual risks into account.

Background and Purpose- We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods- This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0-1). Results- Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68-1.41]; P=0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P>0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06-12.58]; P>0.999), respectively. Conclusions- No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02002325.

BACKGROUND: TIAregistry.org is an international cohort of patients with transient ischemic attack (TIA) or minor stroke within 7 days before enrollment in the registry. Main analyses of 1-year follow-up data have been reported.5 We conducted subanalysis on the baseline and 1-year follow-up data of Japanese patients. METHODS: The patients were classified into 2 groups based on Japanese ethnicity, Japanese (345) and non-Japanese (3238), and their baseline data and 1-year event rates were compared. We also determined risk factors and predictors of 1-year stroke. RESULTS: Current smoking, regular alcohol drinking, intracranial arterial stenosis, and small vessel occlusion; and hypertension, dyslipidemia, coronary artery disease, and extracranial arterial stenosis were more and less common among Japanese patients, respectively. Stroke risk was higher and TIA risk was lower at 1-year follow-up among Japanese patients. The baseline risk factors for recurrent stroke were diabetes, alcohol drinking, and large artery atherosclerosis. Independent predictors of 1-year stroke risk were prior congestive heart failure and alcohol consumption. CONCLUSIONS: The two populations of patients featured differences in risk factors, stroke subtypes, and outcome events. Predictors of recurrent stroke among Japanese patients included congestive heart failure and regular alcohol drinking. Strategies to attenuate residual risk of stroke aside from adherence to current guidelines should take our Japanese-patient specific findings into account.

OBJECTIVE: Direct oral anticoagulants (DOACs) were recently introduced for the clinical use in stroke prevention, and they are reported to show a lower risk of intracerebral hemorrhage (ICH) compared to warfarin. We were interested to know whether there is any change in clinical backgrounds of ICH patients to date. METHODS: From 2010 to 2015, ICH patients admitted to our hospital were consecutively screened (n = 658). Hematoma size was assessed by brain computed tomography images on admission. Outcome was measured by the modified Rankin Scale, and favorable outcome was defined as modified Rankin Scale 0-2. Biennial trends were compared in 3 periods, P1: 2010-2011, P2: 2012-2013, and P3: 2014-2015. RESULTS: The percentage of ICH patients taking antithrombotics had been slightly decreasing (P = .245: [P1] 33.0%, [P2] 27.4%, and [P3] 26.2%). The frequency of patients taking antiplatelets had significantly decreased (P = .001: [P1] 50.7%, [P2] 44.3%, and [P3] 22.8%), and those taking DOACs had significantly increased (P = .001: [P1] 1.4%, [P2] 4.9%, and [P3] 19.3%). Frequency of favorable outcomes in patients taking antithrombotics was slightly increased in P3 compared to P1 and P2 (23.3%, 21.1%, and 21.3%, respectively). There was no significant difference in hematoma size between patients taking warfarin and DOACs. CONCLUSIONS: Number of ICH patients taking antithrombotics has been slightly decreasing and the percentage taking DOACs among ICH has been increasing for 6 years.

BACKGROUND: Since non-vitamin K antagonist oral anticoagulants (NOACs) were released for clinical use, many studies have investigated its effectiveness in stroke prevention. In this study, to determine whether or not there is a difference in outcome in secondary stroke prevention between warfarin and NOACs, patients with embolic stroke with newly prescribed anticoagulants were prospectively analyzed. METHODS: Patients with acute ischemic stroke, who newly started anticoagulant therapy, were consecutively asked to participate in this study. Enrolled patients (76.3 ± 11.0 years old) were classified into warfarin (n = 48), dabigatran (n = 73), rivaroxaban (n = 49), and apixaban (n = 65). The outcome in 1 year was prospectively investigated at outpatient clinic or telephone interview. Recurrence of stroke and death was considered as the critical incidence. RESULTS: The prevalence of risk factors was not different among all medicines. Patients with dabigatran showed significantly younger onset age (P < .001: 72.2 years old) and milder neurologic deficits than patients on other medicines (P < .001). Cumulative incident rates were 7.1%, 15.3%, 19.0%, and 29.7% for dabigatran, apixaban, rivaroxaban, and warfarin, respectively. Dabigatran showed relatively better outcome compared with warfarin (P = .069) and rivaroxaban (P = .055). All patients on NOACs presented lower cumulative stroke recurrence compared with warfarin. CONCLUSION: Even in the situation of secondary stroke prevention, noninferiority of NOACs to warfarin might be demonstrated.

BACKGROUND: Recently, non-vitamin K antagonist oral anticoagulants such as direct thrombin and direct factor Xa inhibitors have been prescribed for prevention of embolic stroke. While in Japan, argatroban, also a direct thrombin inhibitor, is available for the treatment of atherothrombotic stroke patients. This study aimed to explore whether there is any differences between direct thrombin and direct factor Xa inhibitors regarding the inhibiting effect against thrombogenesis in the clinical setting of acute ischemic stroke. METHODS: Acute ischemic stroke patients newly prescribed anti-thrombotic agents were consecutively screened, and 44 patients with single medicine were enrolled (median 72.0 years-old). Blood samples were obtained at 1 and 2 weeks after the medication started. The extent of anticoagulation activity, inflammatory markers and platelet aggregation were assessed. Patients with antiplatelets were used as control. RESULTS: Prescribed antithrombotics were dabigatran (group D: n = 12), apixaban (group A: n = 14) and antiplatelet agents (group P: n = 18). Prevalence of stroke risks and anticoagulation activity were not different between groups D and A. The alteration of inflammatory markers in a week in the group A showed similar trend to those in the group P. The group D presented relatively lower amount of high-sensitive C-reactive protein and higher amount of pentraxin-3 compared with groups A and P. While 88.9% of group P patients showed decreased platelet aggregation activity with adenosine diphosphate, 55.6% of group D and 40.0% of group A presented the inhibition of platelet aggregation activity. CONCLUSIONS: Even in acute ischemic stroke patients, both apixaban and dabigatran equally showed the anticoagulation activity. The reduction of inflammatory response might be prominent in apixaban, whereas the inhibition of platelet aggregation activity might be evident in dabigatran.

Objective In Japan, stroke care is provided through medical cooperation and standardized treatment. However, various factors affect mortality in the hyperacute phase. The present study investigated factors associated with death within 24 h after admission for acute stroke. Methods Among 2335 patients admitted within 24 h after stroke onset from 1 January 2007 to 31 December 2012, a total of 139 deaths occurred. Forty-eight deaths occurred within 24 h after admission. We retrospectively examined the clinical features of these 48 patients. Results The overall mortality rate was 6.0%. When the initial 72-h period was divided into ≤24 h (Period I), >24 to 48 h (Period II), and >48 to 72 h (Period III), deaths were significantly more frequent in Period I than in the other two periods. The frequency of intracerebral haemorrhage (ICH) was also significantly higher in Period I than in the other two periods. Factors significantly associated with death from ICH were systolic blood pressure, hematoma volume, and surgery. Conclusion The mortality rate was low among patients with stroke transported to the authors' medical center within 24 h of onset. Blood pressure management and the timing of determining indications for surgery are important factors in acute haemorrhagic stroke care.

OBJECTIVES: We investigated the effectiveness of clopidogrel loading (CL) treatment compared with usual clopidogrel non-loading (NL) treatment for acute ischemic cerebrovascular disease. METHODS: We screened consecutive 1072 patients with ischemic cerebrovascular disease within 48 hours of symptom onset admitted to our hospital. Eligible patients were divided into the CL group (300 mg on day 1, followed by 50-75 mg once daily) and NL group (50-75 mg once daily). The incidence proportion of neurologic deterioration during hospitalization was compared between the 2 groups using logistic regression analysis. RESULTS: A total of 224 patients, 39 in CL group and 185 in NL group, were enrolled. The frequency of neurologic deterioration did not significantly differ between the 2 groups (risk ratio [95% confidence interval]: 1.47 [.88-2.46]). On the preset subgroup analysis according to stroke subtype, the frequency of neurologic deterioration in CL group was significantly higher in branch atheromatous disease (risk ratio: 2.44 [1.67-3.55]) and was not different statistically in transient ischemic attack (risk ratio: 0). The analysis adjusted by several confounders showed that the incidence proportion of neurologic deterioration was not significantly different in large artery atherosclerosis (adjusted odds ratio: 1.06 [.23-4.84]) as crude analysis. The incidence proportion of adverse events was not significantly different between the 2 groups. CONCLUSIONS: The effect of CL therapy differed by stroke subtypes in preventing neurologic deterioration. CL therapy appeared to be ineffective in branch atheromatous disease. Therefore, the choice of CL therapy should carefully be made according to stroke subtypes.

Fragility of atheromatous plaque in the internal carotid artery can be a risk of brain infarction. The activation of macrophages by oxidative stress and the vulnerability of vascular endothelial cells have been reported to participate in the fragility of atheromatous plaque. Therefore, from the view point of prevention of brain infarction, we investigated the pathological factors which may influence the stabilization of atheromatous plaque. Patients undertaking carotid endoarterectomy (CEA) were continuously screened. Then, 21 samples were obtained from the atheromatous plaques of CEA patients. The expression of connexin (Cx) which composes a gap junction, an intercellular communication organ, was immunohistochemicaly observed. The expression of CD36, an oxidized low-density lipoprotein receptor, was assessed as a marker of oxidative stress. As a result, asymptomatic plaques which were assumed the stable plaques expressed Cx43 along with CD36 expression. In contrast, in the symptomatic plaques, the expression of Cx43 was few and there was almost no coexpression with CD36. The distribution of Cx37 expression was not different between asymptomatic and symptomatic plaques. The expressions of CD36, Cx37 and Cx43 showed no relation to the previous treatment with statins. In conclusion, Cx43 might contribute to the stabilization of atheromatous plaque which is affected by oxidative stress.

Cerebral circulation is known to be protected by the regulatory function against the hypoperfusion that will affect the cognitive function as a result of brain ischemia and energy failure. The regulatory function includes cerebrovascular autoregulation, chemical control, metabolic control, and neurogenic control, and those compensatory mechanisms can be influenced by hypertension, atherosclerosis, cardiac diseases, cerebrovascular diseases and aging. On the other hand, large and/or small infarction, intracranial hemorrhage, subarachnoid hemorrhage, atherosclerosis, amylod angiopathy are also more directly associated with cognitive decline not only in those with vascular cognitive impairment or vascular dementia but also those with Alzheimer's disease.

Poststroke depression (PSD) is a critical complication which might lead to unfavorable outcomes. However, most cases of PSD in the acute phase, during the 2 or 3 weeks following a stroke, are neglected because of the variable comorbid conditions. In this study, aimed at revealing the outstanding symptoms of PSD during the acute phase, consecutive patients with intracranial hemorrhage (ICH) or brain infarction (BI) were asked to fill out a depression questionnaire (Quick Inventory of Depressive Symptomatology Self-Report: QIDS-SR) at 1 week and 1 month following stroke onset. Patients with disturbed consciousness or aphasia were excluded from this study. Forty-nine ICH patients and 222 BI patients completed the QIDS-SR at 1 week and 27 of ICH and 62 of BI at 1 month. The PSD rate was 67% and 46% at 1 week in ICH and BI, respectively. Although sleep disturbance was the most frequent symptom of PSD, psychomotor agitation and appetite disturbance were the most distinguishing symptoms in ICH at 1 week and fatigue at 1 month. On the other hand, most of the depressive symptoms addressed in QIDS-SR were observed in PSD of BI patients both at 1 week and 1 month. In conclusion, while sleep disturbance was a frequent but non-specific symptom, appetite disturbance and fatigue might be critical symptoms to suggest PSD during the acute phase of stroke.

BACKGROUND: It is sometimes difficult to choose anti-thrombotic agents for secondary prevention in stroke patients at high bleeding risk. Recently, Eicosapentaenoic Acid (EPA) was reported to reduce the recurrence of stroke in hypercholesterolemic patients without increasing hemorrhagic risk. In this study, we investigated the features of recurrent stroke patients during EPA medication as secondary stroke prevention. METHODS: Following the approval of the ethical committee, stroke patients in the outpatient clinic were consecutively screened and patients who continuously take EPA were enrolled in this study (n = 71, average age 69.7 yo). Blood sample data was adopted from the latest visit or the admission at the stroke recurrence. According to the previous stroke history, all patients were classified into the hemorrhagic stroke (HS) group (n = 10) and the ischemic stroke, including asymptomatic infarction, (IS) group (n = 61). RESULT: Any stroke recurrence was not observed in the HS group. Whereas, ischemic stroke recurrence was observed in 6 patients in the IS group, although there was no hemorrhagic stroke recurrence. Recurrent stroke patients showed the higher serum level of cholesterol or the renal dysfunction. The stroke subtype of patients were 2 embolic strokes, 3 atherothrombotic infarctions (two were compromised with renal failure and one had insufficient amount of EPA) and one lacunar infarction (who showed high triglyceride level). CONCLUSION: Hemorrhagic stroke was not occurred in our observation of EPA prescribed patients. The clinical features of recurrent stroke patients were the existing complications of dyslipidemia and renal dysfunction.

BACKGROUND: We had reported that, in the acute phase of the brain penetrating artery infarction, patients with branch atheromatous disease (BAD) tended to be worsened compared with the lacunar infarction (LI). Because no prospective study has been reported, we composed a multicenter study (Japan Branch Atheromatous Disease [J-BAD] Registry) in which patients of penetrating artery infarction were prospectively enrolled for exploring the clinical features of BAD. METHODS: From the associated 9 hospitals, acute ischemic stroke patients were asked to be enrolled in the J-BAD Registry and classified into the lenticulostriate arterial (LSA) infarction (n = 124) and the pontine penetrating arterial (PPA) infarction (n = 42) groups. The clinical courses and the repeated magnetic resonance imaging findings were investigated. RESULTS: Neurologic worsening was observed at a significantly higher rate in BAD compared with the LI patients in both the LSA and PPA groups (P < .01, 45.1% versus 22.6% and 46.7% versus 0%, respectively). In the LSA group, the enlargement of the ischemic lesion was significantly more frequent in BAD compared with the LI patients (P < .01, 66.2% and 34.0%, respectively). There was a significant relation between the enlargement of the lesion and the worsening of neurologic deficits (P < .001). Moreover, the clinical features, which predict the lesion enlargement, were BAD and older age. CONCLUSIONS: LSA infarction of BAD diagnosis or older age patients might show an increase of lesion size and a tendency of neurologic worsening. It could be important to discriminate BAD from other ischemic stroke subtypes, in regard to the prediction of prognosis.

BACKGROUND: It is controversial whether taking antiplatelet agents (APs) or anticoagulant agents (ACs) could influence clinical outcome after intracerebral hemorrhage (ICH). METHODS: We retrospectively investigated 557 ICH patients between September 2008 and August 2013. We reviewed patients' characteristics, hematoma volume, deterioration (hematoma expansion, surgical hematoma evacuation, or death), and clinical outcome in modified Rankin Scale. RESULTS: A total of 397 were classified as neither AP nor AC ("Nothing"), 81 as single AP (44 as aspirin [ASA], 22 as clopidogrel or ticlopidine [CLP/TIC], 7 as cilostazol, 8 as dual antiplatelet therapy), 43 as single AC (40 as warfarin, 2 as rivaroxaban, 1 as dabigatran), and 36 as both AP and AC (AP + AC). The clinical outcome was worse in APs than in "Nothing" (P = .021). Among APs, CLP/TIC showed poorer clinical outcome than ASA (P = .020). Deterioration was observed more frequently in AC than in "Nothing" (P < .001) and the clinical outcome was also worse in AC than in "Nothing" (P < .001). AP + AC use resulted in deterioration more frequently than "Nothing" (P < .001) and in poorer outcome than in "Nothing" (P < .001). CONCLUSIONS: The use of antithrombotic agents could be associated with the deterioration after admission and the poor clinical outcome. CLP/TIC use may affect the poor outcome compared with ASA use.

Our objective was to investigate the effect of cilostazol in acute therapy for small vessel stroke patients. The neurologic deficits in some patients of small vessel brain infarction will progress even if a patient takes immediate medical treatments including aspirin or other antiplatelet drugs. In Japan, cilostazol, presenting not only the antiplatelet effect but also the arteriole dilation, is used for treatment of ischemic stroke. In this study, acute stroke patients with small vessel occlusion were treated with cilostazol instead of aspirin in the conventional medication after 2010. Therefore, patients between April 2007 and March 2009 were classified into the conventional group (group-con, n=220), and patients between April 2010 and March 2012 were classified into the cilostazol group (group-cilo, n=230). Enrolled patients were classified into lacunar infarction (LI) and branch atheromatous disease. Progressing stroke was defined as the increase of National Institutes of Health Stroke Scale score of 2 or more within 48 hours. The clinical outcome was assessed by the modified Rankin Scale (mRS) score at 1 month. As the result, the significant reduction in progressing stroke was dominant in the LI of brainstem (P=.01). The length of hospital stay was significantly shorter in the group-cilo compared with the group-con (18.6 and 21.2 days, P=.03). Moreover, mRS score at 1 month was significantly lower in the group-cilo than the group-con (1.9 and 2.3, P=.03). In conclusion, cilostazol reduced the risk of early neurologic deterioration of patients with small vessel brain infarction. It is eagerly desired to conduct a large randomized control trial.

BACKGROUND: The aim of this study was to investigate the clinical features of progressing stroke of pontine infarction as small vessel disease. METHODS: Enrolled 38 acute pontine infarctions were confirmed by magnetic resonance imaging and magnetic resonance angiography at the first and seventh days. Ten patients (26.3%) presented progression (NIH Stroke Scale ≥2 increase within 72 h). RESULTS: Progressing patients showed no relation to the size and the distribution of lesion. Expansion of ischemic lesion showed correlation with basilar artery atherosclerosis. Stable lesion related to delayed worsening. CONCLUSION: These findings suggest that progressing stroke may be caused by not only the worsening of blood flow of ischemic lesion but also delayed neuronal death.

Patients with branch atheromatous disease (BAD) are more likely to experience neurologic deficits compared with those with lacunar infarction (LI), although both disorders are forms of intracranial deep brain infarction. We clinically evaluated patients with BAD (n = 42) and LI (n = 57) to investigate why patients with BAD tend to experience progressing stroke. Patients presenting to our hospital with acute ischemic stroke between April 2008 and March 2009 were screened. LI was defined as an intracerebral lesion <15 mm in diameter and fewer than 3 slices or a lesion within the pontine parenchyma. BAD was defined as an intracerebral lesion of ≥ 15 mm in diameter and more than 3 slices or a lesion extending to the surface of the pontine base observed on diffusion-weighted magnetic resonance imaging. Progressing stroke was defined as a >2-point increase in the National Institutes of Health Stroke Scale within 48 hours of stroke onset. Progressing stroke was significantly more prevalent in the BAD group compared with the LI group (38.1% vs 12.3%). Diabetes mellitus with a high low-density lipoprotein level was significantly prevalent in patients with progressing BAD. When BAD in the cerebrum and BAD in the pons were analyzed separately, a low-density lipoprotein level >140 mg/dL was the most prevalent risk factor for progressing BAD in the cerebrum, and patient age was the strongest risk factor for progressing BAD in the pons. Vascular lesions asvsessed by magnetic resonance angiography were significantly abundant in both progressing LI and BAD. Our findings suggest that BAD may have a poorer prognosis than LI. Poorly controlled diabetes and hyperlipidemia could lead to atherosclerosis of the branch artery, resulting in worsening of BAD.

This study examined the clinical features of 27 acute stroke patients with pulmonary embolism (PE). The primary diagnosis was cerebral infarction (CI) in 12 (0.25%) patients, cerebral hemorrhage (ICH) in 12 (0.94%) and subarachnoid hemorrhage (SAH) in 3 (0.59%). The mortality was 3 (25%), 3 (25%), 1 (33%), respectively. The median (quartile) of National Institutes of Health Stroke Scale was 13.0 (10.0–21.5) in CI, 17.5 (16.0–23.3) in ICH at admission, and the value was comparatively high but varied widely. The onset median time was from 8 to 13.5 days. PE was prone to occur in cases with severe motor paresis in CI and ICH. The activities of daily living was bedridden state in 77.8%. Compared to previous reports, the incidence rate of PE remained nearly the same. PE occurred in CI more than others because CI has difficulty in using anti-thrombotic agents. The mortality rate in PE is still high, so we need to consider the prophylaxis from early phase.

OBJECTIVE: Cerebrovascular lesions (CVLs) are known to play important roles in the pathophysiology underlying Alzheimer's disease (AD), especially in elderly AD cases. The present study was conducted to elucidate the relationship between the CVLs and vascular risk factors (VRFs) in elderly Japanese patients with AD. SUBJECTS AND METHODS: The CVLs such as lacunar infarcts, old microbleeds (OMBs), white matter lesions (WMLs), and occlusive vascular lesions on MRI were analyzed in relation to the risk factors in 120 Japanese patients with probable AD. Their mean age was 75.6 years. The subjects were divided into two age groups: young-old group (YOG) consisting of 55 cases being younger than 75 years and old-old group (OOG) consisting of 65 cases being 75 years or older. RESULTS: In overall analysis, 10 cases (8.3%) showed brain atrophy without CVLs on MRI, 46 cases (38.3%) showed WMLs in addition to the brain atrophy, 61 cases (50.8%) showed lacunar lesions, and 3 cases (2.5%) were diagnosed as having a superficial siderosis. Lacunar infarcts and OMBs were more frequently observed in OOG than in YOG, and were also more frequently observed in those with 2 or more VRFs than those with less than 2 VRFs (p<0.05). The WMLs were more pronounced in OOG, and in those with more VRFs. CONCLUSION: The CVLs including lacunes, WMLs, and OMBs were present more than 90% of elderly Japanese patients with AD. As the severity of CVLs was associated with VRFs and age, VRFs may modify clinical presentation of elderly AD patients.

There have been many reports about the prognosis and risk factors of stroke recurrence following brain infarction (BI). However, little is known about the stroke recurrence after primary intracerebral hemorrhage (PICH). Therefore, we explored the recurrent stroke patients after initial PICH retrospectively, to reveal the critical factors of stroke recurrence. Acute BI (n=4013) and acute PICH patients (n=1067) admitted to the hospital between April 2000 and March 2009 were consecutively screened. PICH patients with a history of ICH and BI patients with a history of ICH were then classified into the ICH-ICH group (n=64, age 70.8±9.5 years) and ICH-BI group (n=52, age 72.8±9.7years), respectively. ICH lesions were categorized into ganglionic and lober types according to the brain magnetic resonance imaging. Subtypes of BI were classified into cardioembolism, large-artery atherosclerosis, small-artery occlusion and others. There was no difference in incidence of risk factors between ICH-ICH and ICH-BI groups. Distribution of initial PICH lesions was significantly abundant in the lobar type in the ICH-ICH group (P<0.01) and in ganglionic type in the ICH-BI group (P<0.02). Age of onset was significantly older in recurrent lobar ICH compared with recurrent ganglionic ICH (P<0.01: 73.6±10.0 and 59.1±9.0 years, respectively). In conclusion, ganglionic ICH patients may have a chance of recurrent stroke in both brain infarction and ganglionic ICH, suggesting the participation of atherosclerosis in intracranial arteries. Lobar ICH patients were older and prone to recurrent lobar ICH, suggesting the participation of cerebral amyloid angiopathy as a risk of stroke recurrence.

Recent case studies have suggested that emotion perception and emotional experience of music have independent cognitive processing. We report a patient who showed selective impairment of emotional experience only in listening to music, that is musical anhednia. A 71-year-old right-handed man developed an infarction in the right parietal lobe. He found himself unable to experience emotion in listening to music, even to which he had listened pleasantly before the illness. In neuropsychological assessments, his intellectual, memory, and constructional abilities were normal. Speech audiometry and recognition of environmental sounds were within normal limits. Neuromusicological assessments revealed no abnormality in the perception of elementary components of music, expression and emotion perception of music. Brain MRI identified the infarct lesion in the right inferior parietal lobule. These findings suggest that emotional experience of music could be selectively impaired without any disturbance of other musical, neuropsychological abilities. The right parietal lobe might participate in emotional experience in listening to music.

BACKGROUND: Although free radicals have been reported to play a role in the expansion of ischemic brain lesions, the effect of free radical scavengers is still under debate. In this study, the temporal profile of ischemic stroke lesion sizes was assessed for more than one year to evaluate the effect of edaravone which might reduce ischemic damage. METHODS: We sequentially enrolled acute ischemic stroke patients, who admitted between April 2003 and March 2004, into the edaravone(-) group (n = 83) and, who admitted between April 2004 and March 2005, into the edaravone(+) group (n = 93). Because, edaravone has been used as the standard treatment after April 2004 in our hospital. To assess the temporal profile of the stroke lesion size, the ratio of the area [T2-weighted magnetic resonance images (T2WI)/iffusion-weighted magnetic resonance images (DWI)] were calculated. Observations on T2WI were continued beyond one year, and observational times were classified into subacute (1-2 months after the onset), early chronic (3-6 month), late chronic (7-12 months) and old (≥13 months) stages. Neurological deficits were assessed by the National Institutes of Health Stroke Scale upon admission and at discharge and by the modified Rankin Scale at 1 year following stroke onset. RESULTS: Stroke lesion size was significantly attenuated in the edaravone(+) group compared with the edaravone(-) group in the period of early and late chronic observational stages. However, this reduction in lesion size was significant within a year and only for the small-vessel occlusion stroke patients treated with edaravone. Moreover, patients with small-vessel occlusion strokes that were treated with edaravone showed significant neurological improvement during their hospital stay, although there were no significant differences in outcome one year after the stroke. CONCLUSION: Edaravone treatment reduced the volume of the infarct and improved neurological deficits during the subacute period, especially in the small-vessel occlusion strokes.

Although the function of astrocytic gap junctions under ischemia is still under debate, increased expression of connexin 43 (Cx43) has been observed in ischemic brain lesions, suggesting that astrocytic gap junctions could provide neuronal protection against ischemic insult. Moreover, different connexin subtypes may play different roles in pathological conditions. We used immunohistochemical analysis to investigate alterations in the expression of connexin subtypes in human stroke brains. Seven samples, sectioned after brain embolic stroke, were used for the analysis. Data, evaluated semiquantitatively by computer-assisted densitometry, was compared between the intact hemisphere and ischemic lesions. The results showed that the coexpression of Cx32 and Cx45 with neuronal markers was significantly increased in ischemic lesions. Cx43 expression was significantly increased in the colocalization with astrocytes and relatively increased in the colocalization with neuronal marker in ischemic lesions. Therefore, Cx32, Cx43, and Cx45 may respond differently to ischemic insult in terms of neuroprotection.

Only a few reports have discussed the detailed clinical symptoms and pathogenesis of bilateral thalamic infarction. The thalamus is composed of different functional nuclei and supplied by vessels containing several variations from the main arteries, leading to difficulty in the precise evaluation of bilateral thalamic infarction. In the present study, we assessed the prognosis of bilateral thalamic infarction based on the distribution of stroke lesions. From among the consecutive ischemic stroke patients admitted to hospital between April 2001 and March 2005, cases of acute bilateral thalamic infarction were selected for this study (n=9; 65.1±13.6 y.o.). The stroke lesions and vascular abnormalities were investigated by magnetic resonance imaging and magnetic resonance angiography on admission. Outcome was evaluated from the modified Rankin scale (mRS) at discharge. Good outcome patients (mRS 0-2; n=5) showed memory disturbance, cognitive impairment and hypersomnia. On the other hand, quadriplegia, oculomotor disturbance and bulbar palsy were observed in the poor outcome patients (mRS ≥4; n=4). The critical features of a poor outcome were the age at onset (72.0±15.3 vs. 58.2±11.9 y.o.), inclusion of brainstem lesions and total occlusion of the basilar artery. In conclusion, older age at onset and/or basilar artery occlusion may be critical factors for predicting a poor outcome in bilateral thalamic infarction cases.<br>

A 53-year-old right-handed woman was admitted to a hospital with a seizure, exhibiting loss of consciousness and paroxysmal myoclonic movement. MRI showed no abnormalities of her brain. Electroencephalography revealed sporadic sharp and slow wave complexes, starting from the right central region. Cerebral perfusion SPECT revealed increased blood supply in the right hemisphere. She received diagnosis of epilepsy and was treated with phenytoin. After she regained her consciousness, she had no voice and presented with left hemiparesis which was interpreted to be Todd's palsy. She gradually recovered in using her voice, to full normalization of affective prosody in 11 days. The left hemiparesis recovered first in the upper and later in the lower extremities. Her symptoms could be interpreted to be vocal and prosodic disturbance, but not aphasia, because she could understand speach and communicate with writing. The lesions responsible for prosodic deficit are still controversial. The symptoms observed and the findings obtained may indicate that the deficiency of the affective prosody may be caused by the dysfunction of the medial surface of the non-dominant frontal lobe in this case.

Purpose : Patients with primary intracerebral hemorrhage (PICH) frequently demonstrate microbleeds (MB) on gradient-echo T2*-weighted MR images (T2*WI) . We assessed the clinical and radiologic differences between PICH with and without MB. Methods : We studied 174 consecutive patients with PICH who underwent both conventional MRI and T2* WI. Results : MB were observed in 65.5% of patients and ranged in number from 1 to 61. The locations of the MB lesions were most commonly in the cortex/subcortex (39.6%). Age, sex, hypertension, diabetes mellitus, hyperlipidemia, blood pressure on admission, Japan stroke scale on admission and at discharge, and hematoma size of PICH were not significantly correlated with either the MB or non-MB groups. Medication with antithrombotics (antiplatelets and/or anticoagulants), lacunes, and advanced leukoaraiosis (LA) were common in patients with MB. On logistic regression analysis, advanced LA was an independent risk factor associated with the presence of MB in patients with PICH (odds ratio, 2.20; 95% confidence interval, 1.06-3.81). Discussion : MB with PICH were associated MR findings of small artery disease, especially the presence of LA. Patients with MB showed a higher incidence of taking antithrombotics. Lacunar infarction and LA have been suggested to indicate a higher risk of bleeding under antithrombotics. Screening of candidates with MRI findings such as MB, LA and lacunes may be useful when selecting antithrombotic medication for ischemic stroke patients. PICH patients with MB who were associated with small artery disease, in particular the presence of LA with MB, revealed a higher incidence of taking antithrombotics.

Astrocytes secrete cytokines and neurotrophic factors to neurons, consistent with a neurosupportive role for astrocytes. However, in ischemic or metabolic insults, the function of astrocytic gap junctions composed mainly from connexin43 (Cx43) remains controversial. We have previously shown that heterozygous Cx43 null mice subjected to middle cerebral artery occlusion exhibited significantly enhanced stroke volume and apoptosis compared to wild-type mice. In this study, we used mice in which the human GFAP promoter-driven cre transgene deletes the floxed Cx43 gene in astrocytes, excluding the effects from reduced Cx43 expression in many other cell types as well as astrocytes. We induced focal brain ischemia in mice lacking Cx43 in astrocytes [Cre(+)] and control littermates [Cre(-)]. Cre(+) mice showed a significantly increased stroke volume and enhanced apoptosis, detected by terminal dUTP nick-end labeling and caspase-3 immunostaining, compared to Cre(-) mice. Inflammatory response assessed by the microglial marker CD11b was amplified in the penumbra of Cre(+) mice compared to that of Cre(-) mice. Our results suggest that astrocytic gap junctions could be important for the regulation of neuronal apoptosis and the inflammatory response after stroke. These findings support the view that astrocytes play a critical role in neuroprotection during ischemic insults.

Gap junctions are intercellular channels which directly connect the cytoplasm between neighboring cells. In the central nervous system (CNS) various kinds of cells are coupled by gap junctions, which play an important role in maintaining normal function. Neuronal gap junctions are involved in electrical coupling and may also contribute to the recovery of function after cell injury. Astrocytes are involved in the pathology of most neuronal disorders, including brain ischemia, Alzheimer's disease and epilepsy. In the pathology of brain tumors, gap junctions may be related to the degree of malignancy and metastasis. However, the role of connexins, gap junctions and hemichannels in the pathology of the diseases in the CNS is still ambiguous. Of increasing importance is the unraveling of the function of gap junctions in the neural cell network, involving neurons, astrocytes, microglia and oligodendrocytes. A better understanding of the role of gap junctions may contribute to the development of new therapeutic approaches to treating diseases of the CNS.

Although diabetes mellitus (DM) has been found to be a strong risk factor for ischemic stroke and is correlated with the worst of outcomes, it has yet to be determined whether or not the stroke subtypes and distribution of ischemic lesions differ in patients with DM as compared to other ischemic stroke patients. We studied 215 consecutive patients with first-time episodes of ischemic stroke at Kyoto Second Red Cross Hospital. Patients with cardiogenic embolism were excluded. MRI examinations were performed on all patients and 158 of the patients underwent cerebral angiography. The patients were classified into 4 groups according to their symptomatic lesions : 118 patients with lacunar infarcts, 62 with non-lacunar infarcts in the supratentorial region, 20 with brainstem infarcts, and 15 with TIAs. The distribution of ischemic lesions, based on the MRIs, was subsequently evaluated for all patients. The lesions included lacunar infarcts (3-15 mm in diameter), cortical and subcortical non-lacunar infarcts, brainstem infarcts, and cerebrallar infarcts. The lacunar infarcts were further divided into 2 subgroups : those located in the territory of the lenticulostriate and subcortical perforating arteries, and those in the thalamoperforating and thalamogeniculate arteries. The brainstem infarcts were also divided into 2 subgroups : the branch atheromatous type (infarcts extending to the surface of the pontine basis), and the lipohyalinosis type (infarcts located within the pons, but not extending to the pontine surface). The relationship between the distribution of ischemic lesions and risk factors, including hypertension (HT), DM, hyperlipidemia (HL), smoking (SM), and heart disease, was investigated. The complication rate of DM was significantly higher in patients with pontine infarcts of the branch atheromatous type than in those without pontine lesions. In contrast, the complication rates of HT, HL, SM, and heart disease were not statistically different between the two groups. The numbers of lacunae were counted, and classified according to the following scheme : 0 (absent), single lacuna (one lacuna), and multiple lacunae (more than two lacunae). Although multiple lacunae, in both the lenticulostriate artery and thalamoperforant artery territories, were found to be significantly correlated with HT, there was no correlation with DM, HL, or SM. Non-lacunar supratentorial infarcts, and cerebellar infarcts showed no correlation with HT, DM, HL, or SM. The stenotic lesions in the extracranial and intracranial arteries identified by cerebral angiography were classified into 4 groups : Grade 0, <30% stenosis ; Grade 1, 30-60% ; Grade 2, 60-99% ; and Grade 3, occlusion. Although higher-grade stenotic lesions tended to be correlated with aging, such lesions were not significantly correlated with other risk factors. DM was also correlated with pontine infarcts of the branch atheromatous type. However, DM showed no correlation with brainstem infarcts of the lipohyalinosis type, thalamic lacunae, or cerebellar infarcts. It was thus not possible to conclude that all infarcts within the territory of vertebrobasilar arteries were associated with DM. The mechanism whereby DM is associated with such lesions requires further clarification.

Purpose and Method : In order to prevent stroke in perioperative period of cardiovascular surgery, we analyzed silent cerebrovascular factors. Seventy-seven patients with Coronary Artery Bypass Graft Surgery (CABG) and forty-three patients with other cardiac operations (non-CABG) were recruited and evaluated by MRI, MRA and cervical duplex ultra-sonography.<BR>Result : The frequency of the silent brain infarction in CABG group (49.4%) was not statistically significant from that in non-CABG group (41.9%). In both groups, almost all of lesions were lacunar infarctions locating in deep carebral white matter.<BR>Severe stenosis or occlusive lesions in intra and/or extracranial major arteries were more frequently found in CABG group than in non-CABG group (29.9% vs 11.6%, p=0.026). The intracranial vascular lesions rather than extracranial ones were more predominantly revealed in our series.<BR>Conclusion : To reduce the peri-and postoperative complications of patients underwent cardiovascular surgery, preoperative evaluation of stenotic vascular lesions in cervical and intracranial areas is very important.