Cerebral Microbleeds With Atrial Fibrillation After Ablation Therapy.

BACKGROUND: The prevalence of cerebral microbleeds (CMBs) is significantly higher in patients with atrial fibrillation (AF) than in those without AF. CMBs in patients with AF have been reported to be primarily of the lobar type, but the exact cause of this remains unknown. We investigated the possibility that hemorrhagic transformation of embolic microinfarction can account for de novo lobar CMBs. METHODS: A total of 101 patients who underwent ablation therapy for AF were prospectively registered, and 72 patients completed the assessment with MRI 6 months after catheter ablation. Brain MRI, including diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI), were examined at 1-3 days (baseline) and 6 months after catheter ablation. We quantitatively evaluated the spatial and temporal distribution of embolic microinfarctions and de novo CMBs. RESULTS: Of the 101 patients, 68 were enrolled in this study. Fifty-nine patients (86.8%) showed embolic microinfarctions on baseline DWI immediately after catheter ablation. There were 137 CMBs in SWI, and 96 CMBs were of the lobar type. Six months later, there were 208 CMBs, including 71 de novo CMBs, and 60 of 71 (84.5%) were of the lobar type. Of the 71 de novo CMBs, 56 (78.9%) corresponded to the location of previous embolic microinfarctions found on baseline DWI. The platelet count was significantly lower and hematocrit/hemoglobin and Fazekas score were higher in the group with de novo CMBs than in the group without de novo CMBs. CONCLUSION: De novo CMBs frequently appeared after catheter ablation therapy. Our results suggest that embolic microinfarction can cause lobar CMBs.

Brain magnetic resonance imaging and cognitive alterations after ablation in patients with atrial fibrillation.

Catheter ablation is an important non-pharmacological intervention for atrial fibrillation (AF), but its effect on the incidence of asymptomatic cerebral emboli and long-term effects on cognitive function remain unknown. We prospectively enrolled 101 patients who underwent AF ablation. Brain magnetic resonance imaging (MRI) (72 patients) and neuropsychological assessments (66 patients) were performed 1-3 days (baseline) and 6 months after ablation. Immediately after ablation, diffusion-weighted MRI and 3-dimensional double inversion recovery (3D-DIR) detected embolic microinfarctions in 63 patients (87.5%) and 62 patients (86.1%), respectively. After 6 months, DIR lesions disappeared in 41 patients. Microbleeds (MBs) increased by 17%, and 65% of the de novo MBs were exactly at the same location as the microinfarctions. Average Mini-Mental State Examination scores improved from 27.9 ± 2.4 to 28.5 ± 1.7 (p = 0.037), and detailed neuropsychological assessment scores showed improvement in memory, constructional, and frontal lobe functions. Ejection fraction, left atrial volume index and brain natriuretic peptide level improved from baseline to 3-6 months after ablation. Despite incidental microemboli, cognitive function was preserved 6 months after ablation.

Pre-stroke cognitive impairment in acute ischemic stroke patients predicts poor functional outcome after mechanical thrombectomy.

OBJECTIVE: Several studies have investigated the predictors of functional outcome in patients with ischemic stroke after mechanical thrombectomy (MT). However, it is not clear whether pre-stroke cognitive (PSC) impairment is associated with the functional outcome of patients treated with MT. METHODS: We enrolled 113 patients treated with MT from December 2016 to November 2018. PSC was evaluated using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Poor outcome was defined as a modified Rankin Scale score of 3-6. We compared the clinical characteristics between the groups with poor outcome (n = 61) and good outcome (n = 52) to determine if PSC could be a predictor of poor outcome. RESULTS: IQCODE was significantly higher in the group with poor outcome than good outcome (3.34 vs. 3.13, P = 0.017). Moreover, the following metrics differed between those two groups: age (75.9 vs. 71.6 years old, P = 0.010), the percentage of females (39.9% vs. 17.3%, P = 0.009), the percentage with hypertension (72.1% vs. 44.2%, P = 0.003), National Institutes of Health Stroke Scale (NIHSS) score on admission (20 vs. 11, P < 0.001), and no successful recanalization (24.5% vs. 7.7%; P = 0.025). Multivariable logistic regression analysis demonstrated that PSC (OR: 5.59; 95% CI: 1.55-23.47), history of hypertension (OR: 3.33; 95% CI: 1.29-9.11), no successful recanalization (OR: 5.51; 95% CI: 1.49-25.03), and NIHSS score on admission (OR: 1.14; 95% CI: 1.07-1.22) were associated with poor outcome 3 months after stroke onset. CONCLUSIONS: PSC was significantly and independently associated with poor functional outcome in patients treated with MT.

Elevated cardio-ankle vascular index may be related to future stroke risk in Japanese subjects.

BACKGROUND: The cardio-ankle vascular index (CAVI) has been proposed as a useful parameter for arteriosclerotic diseases. However, whether it is associated with stroke risk in Japanese subjects remains unclear. METHODS: In total, 280 Japanese subjects (92 females, 52.6 ± 5 years old) underwent a medical check-up. CAVI value and risk factors for arterial dysfunction were evaluated; the predicted 10-year stroke risk was measured by the Japan Public Health Center study. RESULTS: Age, sex, body mass index, and systolic blood pressure were significant independent predictors of CAVI. CAVI values were significantly elevated in the high, compared with the medium-low and low predicted risk groups. A significant odds ratio (OR) for the high-risk group was noted in the highest quartile of CAVI values (OR, 14.67; 95% confidence interval [CI], 3.17-68.0), compared with the lowest quartile, after adjusting for potential confounders. A significant OR for very high predicted stroke risk was also found for each quartile increase (OR, 3.04; 95% CI, 1.87-4.94) and 1-standard deviation increase (OR, 2.24; 95% CI, 1.52-3.30) in CAVI value. CONCLUSION: Elevated CAVI values were related to an elevated predicted stroke risk, suggesting that CAVI could be a suitable surrogate marker for finding subjects at an increased risk of first-ever stroke.

Early Cognitive Impairment after Minor Stroke: Associated Factors and Functional Outcome.

OBJECTIVES: Evaluation of cognitive status is not performed routinely in the acute stroke setting. This study aimed to evaluate the frequency of early cognitive impairment in patients with minor ischemic stroke, analyze the factors associated with early cognitive impairment, and assess functional outcomes. METHODS: In this prospective study, 112 consecutive patients with acute minor ischemic stroke were enrolled. Neuroimages were assessed for semiquantitative evaluation of brain atrophy and small vessel disease (SVD) markers. Cognitive performance was measured within 5 days of onset using Montreal Cognitive Assessment (MoCA) scores. Functional outcome analyses were adjusted for demographic variables, premorbid cognitive status, education level, vascular risk factors, neuroimaging characteristics, stroke severity, and MoCA scores. RESULTS: The median MoCA score was 22, and 63% of patients had cognitive impairment. Factors independently associated with cognitive impairment were education (odds ratios [OR], .79; confidence intervals [CI], .63-.99), smoking (OR, .26; 95%CI, .073-.89), and temporal horn atrophy (OR, 4.73; 95% CI, 1.66-13.49). Factors independently associated with poor functional outcome were total MoCA score (OR, .78; 95%CI, .62-.95) and the sum of 4 MoCA subscores (visuospatial/executive, attention, language, and orientation; OR, .72; 95%CI, .53-.92). The cutoff value of the sum of 4 MoCA subscores for predicting poor outcome was 13 points with 76.5% sensitivity and 81.1% specificity. CONCLUSIONS: Early cognitive impairment was common after minor ischemic stroke and was associated with preexisting temporal horn atrophy but not SVD markers. The sum of 4 MoCA subscores was useful in predicting the functional outcome.

Early Cognitive Assessment Following Acute Stroke: Feasibility and Comparison between Mini-Mental State Examination and Montreal Cognitive Assessment.

OBJECTIVES: Cognitive assessment is not performed routinely in the acute stroke setting. We investigated factors associated with cognitive impairment and the differences between the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores in patients with acute stroke. METHODS: In this prospective study, 881 consecutive patients (median age, 73 years) with acute stroke were enrolled. Clinical characteristics, such as education, vascular risk factors, premorbid cognitive status using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), and stroke severity, were assessed. Cognitive performance was measured using MMSE and MoCA within 5 days of stroke onset. RESULTS: Both MMSE and MoCA were feasible in 621 (70.5%) patients. Factors independently associated with nonfeasibility were age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.02-1.08), IQCODE score (OR: 1.02; 95%CI: 1.00-1.04), and National Institutes of Health Stroke Scale (NIHSS) score (OR, 1.16; 95%CI, 1.12-1.20). Impaired MoCA (with a cut-off <26/30) performance was observed in 544 of 621 (87.6%) patients. Factors independently associated with cognitive impairment were age (OR: 1.06; 95%CI: 1.03-1.10) and NIHSS score (OR: 1.34; 95%CI: 1.14-1.57). Eighty percent of patients with normal MMSE scores had an impaired MoCA score (MMSE-MoCA mismatch). The differences were highest in the visuospatial (94.8% versus 65.3%; P < .0001), recall (76.6% versus 35.6%; P < .0001), abstraction (82.5% versus 49.8%; P < .0001), and language (72.3% versus 65.9%; P < .0001) domains between the normal MMSE and MoCA group and MMSE-MoCA mismatch group. CONCLUSIONS: The MoCA can be particularly useful in patients with cognitive deficits undetectable on the MMSE in the acute stroke phase.

Successful endovascular recanalization of massive cerebral venous sinus thrombosis in a patient with tuberous sclerosis and protein S deficiency: a case report.

Here, we report the case of a 27-year-old woman with tuberous sclerosis complex who underwent successful endovascular intervention for cerebral venous thrombosis at the superior sagittal sinus. She had protein S deficiency and a long-term history of anemia caused by menorrhagia from uterine fibroids, possibly leading to a hypercoagulable state. Cerebral venous sinus thrombosis accounts for ~0.5-1% of all strokes. Several cases of venous thrombosis in patients with tuberous sclerosis complex and protein S or protein C deficiency have been reported, but further studies are needed to identify whether an association of this rare combination may be explained.

Ischemic stroke during anticoagulant interruption by healthcare professionals in stroke patients with atrial fibrillation.

BACKGROUND: Anticoagulant therapy often requires temporary interruption. Nevertheless, the frequency and clinical characteristics of stroke patients who develop stroke during anticoagulant interruption are not fully known. METHODS: From March 2011 through May 2017, consecutive acute ischemic stroke patients with AF who were admitted to our stroke unit were retrospectively recruited. Patients who developed ischemic stroke during anticoagulant interruption were defined as those who developed ischemic stroke within 30 days from anticoagulant interruption. The frequency and clinical characteristics of patients during anticoagulant interruption were analyzed. RESULTS: A total of 561 patients with AF and acute ischemic stroke (237 women; median age 78 [IQR 71-85] years) were admitted during the study period. Of these, 21 (3.7%, 12 patients discontinued vitamin K antagonist [VKA] and 9 discontinued direct oral anticoagulants [DOACs]) patients were admitted during the period of anticoagulant interruption. Severity and functional outcomes in stroke patients during anticoagulant interruption were not different from those without anticoagulant treatment. The number of days between anticoagulant interruption and stroke onset was shorter in patients who discontinued DOACs (3 [3-5] days) than in those who discontinuedVKAs (10 [7-20] days, p = .004). The major reason for interruption was planning of invasive procedures (52%). Guideline deviations were suspected in 82% of such cases. CONCLUSION: Patients developing stroke during anticoagulant interruption accounted for 3.7% of stroke patients with AF. Strokes occurred relatively early after interruption, especially in patients who discontinued DOACs. Guideline deviations was frequent.

Characteristics of Acute Spontaneous Intracerebral Hemorrhage in Patients Receiving Oral Anticoagulants.

OBJECTIVE: We investigated the precise clinical and radiologic characteristics of intracerebral hemorrhage associated with direct oral anticoagulant use. METHODS: Patients with acute spontaneous intracerebral hemorrhage admitted to our department from September 2014 to November 2017 were retrospectively analyzed. Clinical and neuroradiological characteristics of patients with direct oral anticoagulant-related intracerebral hemorrhage, and effects of prior treatment on the severity at admission and on outcome at discharge were assessed. RESULTS: Of the 301 enrolled patients (103 women; median age 68 years), 261 received no oral anticoagulants (86.8%), 20 received warfarin (6.6%), and 20 received direct oral anticoagulants (DOACs) (6.6%). Median initial National Institutes of Health Stroke Scale scores differed significantly among the groups (P = .0283). Systolic blood pressure (P = .0031) and estimated glomerular filtration rate (P = .0019) were significantly lower in the oral anticoagulant-related intracerebral hemorrhage group than in other groups. Total small vessel disease scores were significantly higher in the oral anticoagulant-related intracerebral hemorrhage group than in the warfarin group (P = .0413). Multivariate analysis revealed that prior oral anticoagulant treatment (odds ratio: 0.21, 95% confidence interval: 0.05-0.96, P = .0445) was independently negatively associated with moderate-to-severe neurological severity (stroke scale score ≥10) after adjusting for intracerebral hemorrhage location and various risk factors. There were significant differences in hematoma volume in the basal ganglia (P = .0366). CONCLUSIONS: DOAC-related intracerebral hemorrhage may occur particularly in patients with a high risk of bleeding; however, they had a milder initial neurological severity than those with warfarin-related intracerebral hemorrhage, possibly due to relatively smaller hematoma volume, especially in the basal ganglia.

The Prevalence of and Factors Related to Vascular Hyperintensity on T1-Weighted Imaging in Acute Ischemic Stroke.

BACKGROUND: Thrombus visualization in patients with acute ischemic stroke has been detected and reported using various imaging modalities. T1-weighted imaging (T1-WI) can depict thrombi as hyperintense signals within vessels. Moreover, in addition to thrombi, T1-WI hyperintensities in arteries may suggest arterial dissection. However, the frequency of and factors related to the T1-hyperintense vessel sign (T1-HVS) are not fully known. The aim of this study was to clarify the prevalence of and related factors for the T1-HVS in patients with acute ischemic stroke. METHODS: From September 2014 through December 2015, consecutive acute ischemic stroke patients who were admitted to our stroke unit within 7 days from symptom onset were retrospectively recruited from the prospective registry. A T1-HVS was defined as the presence of a hyperintense signal, with intensity higher than surrounding brain, within the vessel lumen. Moreover, T1-HVSs were separated into filled T1-HVSs (hyperintensity fills whole vessel lumen) and non-filled T1-HVSs. The frequency of the T1-HVS and the timing of emersion and the relationship between the presence of the T1-HVS and arterial occlusion were assessed. RESULTS: A total of 399 patients (139 women; median age 73 years; National Institutes of Health Stroke Scale score 3) were enrolled in the present study. Of these, 327 (82%) patients had T1-WI on admission. Two hundred and sixty-seven (67%) subjects had at least one follow-up T1-WI (median 6 days after admission), and 134 (34%) cases had ≥2 follow-up T1-WI examinations. The T1-HVS was observed in 18 patients during admission; therefore, the frequency of the T1-HVS in acute ischemic stroke patients was 4.5% (95% CI 2.5-6.5%). All but one (94%) of the T1-HVSs were first observed on follow-up imaging, and the median number of days from onset to T1-HVS appearance was 9. For patients having initial major artery occlusion and follow-up MRI (n = 95), sensitivity and specificity of the T1-HVS for persistent arterial occlusion on follow-up MR angiography were 22 and 100%, respectively. T1-HVS persisted for a few months and then normalized. Although there were no significant differences between filled and non-filled T1-HVS, more patients with non-filled T1-HVS had arterial dissection (43%) than those with filled T1-HVS (9%, p = 0.245). CONCLUSION: The T1-HVS was observed in 4.5% of acute ischemic stroke patients. T1-HVSs appeared in the subacute phase in arteries with persistent occlusion and remained for a few months.

Albuminuria predicts early neurological deterioration in patients with acute ischemic stroke.

BACKGROUND: Reduced glomerular filtration rate (GFR) and albuminuria have been independently associated with an increased risk of stroke and unfavorable long-term outcomes. However, the association between GFR, albuminuria, and early neurological deterioration (END) in patients with ischemic stroke has not been well studied to date. We therefore investigated the ability of estimated GFR (eGFR) and albuminuria to predict END in patients with acute ischemic stroke. METHODS: We retrospectively enrolled 294 patients that were admitted to our stroke center with acute ischemic stroke between January 2011 and September 2012. General blood and urine examinations, including eGFR and urinary albumin/creatinine ratio (UACR) measurements, were performed on admission. Kidney dysfunction was defined by a low eGFR value (<60mL/min/1.73m2) and/or increased albuminuria (≥30mg/g creatinine). END was defined as a ≥2-point increase in the National Institutes of Health Stroke Scale (NIHSS) score within 7days after admission. RESULTS: Kidney dysfunction was diagnosed in 200 of the 294 patients (68.0%). END was observed in 60 patients (20.4%). Age, blood glucose level on admission, UACR on admission, and NIHSS score on admission were significantly associated with END, while no relationship between eGFR on admission and END was identified. A multivariable logistic regression analysis showed that END was positively associated with high UACR (≥39.6mg/g creatinine) and a high NIHSS score (≥6 points). CONCLUSIONS: Our data suggest that high UACR on admission may predict END in patients with acute ischemic stroke. Larger prospective studies are required to validate the correlation between albuminuria and END.

Low free triiodothyronine predicts poor functional outcome after acute ischemic stroke.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the association of admission serum thyroid hormone concentration with clinical characteristics and functional outcomes in patients after acute ischemic stroke. METHODS: We retrospectively enrolled 398 consecutive patients admitted to our stroke center between July 2010 and April 2012. Serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were evaluated upon admission. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) upon admission and the modified Rankin Scale (mRS) upon discharge. Poor outcome was defined as a mRS score of 3-5 or death (mRS score 6). Separate analyses were conducted according to outcome and quartile serum FT3 concentration. RESULTS: In total, 164 patients (41.2%) demonstrated a poor outcome. Age, male gender, blood glucose level, arterial fibrillation, dyslipidemia, smoking, NIHSS score, cardioembolic stroke type, and periventricular hyperintensities, but not FT4 or TSH, were significantly associated with poor functional outcome. Furthermore, poor functional outcome was independently associated with low FT3 (<2.29pg/mL). In comparisons between FT3 quartiles (Q1 [≤2.11pg/mL], Q2 [2.12-2.45pg/mL], Q3 [2.46-2.77pg/mL], Q4 [≥2.78pg/mL]), patients with poor outcomes were more frequent in Q1 than in Q4 after multivariate adjustment. Death was more frequent in Q1 than in Q4 after adjustment for risk factors and comorbidities, but this difference was non-significant after additional adjustment for age and NIHSS score. CONCLUSIONS: Our data suggest that a lower FT3 value upon admission may predict a poor functional outcome in patients with acute ischemic stroke. Further large-scale prospective studies are required to clarify the role of thyroid hormone in the acute phase of ischemic stroke.

Feasibility of using magnetic resonance imaging as a screening tool for acute stroke thrombolysis.

BACKGROUND: Feasibility of performing MRI first for suspected hyperacute stroke patients in real-world practice has not been fully examined. Moreover, most past studies of reducing door-to-needle time (DNT) in intravenous thrombolysis were conducted using CT. The aim of this study was to evaluate the feasibility of an MRI-first policy and examine the effects of a quality improvement (QI) process for reducing DNT using MRI. METHODS: From January 2014 to August 2015, consecutive acute stroke patients who were treated with thrombolysis were prospectively enrolled into the present study. In principle, multimodal 1.5T-MRI was performed first for patients with suspected acute stroke. A step-by-step QI process for decreasing DNT, including prenotification by the emergency medical service, limiting the MRI sequence, and introduction of a rapid examination tool, was also implemented during this period. Time metrics for thrombolysis were compared between specific time periods. RESULTS: A total of 73 patients (27 women; median age 74years) were included in the present study. More than 80% of the patients were screened with MRI. More patients were managed with the MRI-first policy in the late phase (p=0.018). DNT (83min in the early phase, 68min in the middle phase, and 54min in the late phase, p<0.001) was significantly reduced across phases. The percentage of patients with DNT<60min increased significantly across time periods (p<0.001). CONCLUSION: An MRI-first policy was feasible, and DNT was substantially reduced with a QI process. This process may be applicable to other hospitals.

Aortic arch atherosclerosis in ischaemic stroke of unknown origin affects prognosis.

BACKGROUND: Cerebral infarction of unknown origin at admission accounts for half of all cerebral infarction cases in some institutions. However, the factors associated with cerebral infarction prognosis have not been sufficiently examined. Here, we investigated whether aortic arch plaques (AAPs) on transoesophageal echocardiography (TOE) were associated with the prognosis of cerebral infarction of unknown origin at admission. METHODS: Of 571 patients who were hospitalised between June 2009 and September 2011, 149 (age: 67 ± 14 years; 95 men) with cerebral infarctions of unknown origin at admission underwent TOE and were enrolled in this study. We examined their clinical characteristics, the incidence of intermittent atrial fibrillation detected on 24-hour electrocardiography, and the echographic findings of the carotid artery in the hospital. A poor prognostic outcome was defined as a modified Rankin Scale score of ≥3 after 90 days. RESULTS: In all, 110 patients (74%) showed good prognoses and 39 patients (26%) showed poor outcomes. A National Institutes of Health Stroke Scale score of >6 on admission [odds ratio (OR) = 6.77; 95% confidence interval (CI): 2.59-18.8; p < 0.001] and AAPs of ≥4 mm (OR = 2.75; 95% CI: 1.19-6.91; p = 0.024) showed significant associations with a poor prognosis of cerebral infarction of unknown origin at admission. CONCLUSIONS: Thick AAPs could be a factor in the prediction of a poor prognosis of cerebral infarction of unknown origin at admission. The establishment of international standards for aortogenic brain embolisms is required. Future prospective studies should examine cerebral infarctions of unknown origin.

Asymmetric dimethylarginine is related to the predicted stroke risk in middle-aged Japanese men.

BACKGROUND: Asymmetric dimethylarginine (ADMA) has recently been investigated as a risk marker for cardio- and cerebrovascular diseases. However, whether ADMA levels are related to the risk of stroke in the Japanese general population remains unclear. METHODS: We examined 769 Japanese men (mean age, 47 ± 5 years) undergoing health examinations. Each subject's ADMA level and various vascular risk factors were assessed; the predicted 10-year stroke risk was calculated using the point-based prediction model from the Japan Public Health Center Study. RESULTS: In a multiple linear regression analysis, age, body mass index, estimated glomerular filtration rate, and current smoking status were significant independent determinants of ADMA levels. A significant odds ratio (OR) for high predicted stroke risk (10-year risk ≥ 5%)was noted in the highest quartile of ADMA levels (OR, 2.47; 95% CI, 1.002-6.07), compared with the lowest quartile, after adjusting for potential confounding factors. A significant OR for high predicted stroke risk was also found for each standard deviation increment in ADMA level (adjusted OR, 1.46; 95% CI, 1.10-1.92). CONCLUSION: Elevated ADMA levels were significantly associated with an increased predicted stroke risk, suggesting that measuring ADMA levels may be useful for identifying middle-aged Japanese men with a high risk of stroke.

The asymmetric dimethylarginine level is associated with the predicted stroke risk in Japanese women.

AIM: Asymmetric dimethylarginine(ADMA) has recently been investigated as a risk marker for cardio- and cerebrovascular diseases. However, it is not currently known whether the ADMA levels are related to the risk of stroke in Japanese women. METHODS: We examined 192 Japanese women(mean age, 55±9 years, range, 40-80 years) who underwent health examinations. The ADMA level and various vascular risk factors of each subject were assessed, and the predicted 10-year stroke risk was calculated using the point-based prediction model provided by the Japan Public Health Center study. RESULTS: In a correlation coefficient analysis, age was found to be the only factor significantly correlated with the ADMA level. A significant odds ratio (OR) for a high predicted stroke risk(10-year risk, ≥5%) was noted in the highest ADMA level tertile(6.24; 95% CI, 1.13-34.5; p=0.036) compared with the lowest tertile, after adjusting for potential confounding factors. A significant OR for a high predicted stroke risk was also found for each increment in the ADMA tertile and standard deviation(adjusted OR, 2.42; 95% CI, 1.09-5.34; p=0.029; and 2.51; 95% CI, 1.24-5.11; p=0.011, respectively). CONCLUSIONS: An elevated ADMA level is significantly associated with an increased predicted stroke risk, suggesting that measuring the ADMA level is useful for identifying Japanese women with an elevated stroke risk.

Continuous oral administration of atorvastatin ameliorates brain damage after transient focal ischemia in rats.

AIMS: Pre-treatment with statins is known to ameliorate ischemic brain damage after experimental stroke, and is independent of cholesterol levels. We undertook pre- vs post-ischemic treatment with atorvastatin after focal cerebral ischemia in rats. MAIN METHODS: Male Sprague-Dawley rats underwent transient 90-min middle cerebral artery occlusion (MCAO). Atorvastatin (20mg/kg/day) or vehicle was administered orally. Rats were divided into vehicle-treated, atorvastatin pre-treatment, atorvastatin post-treatment, and atorvastatin continuous-treatment groups. In the pre-treatment, rats were given atorvastatin or vehicle for 7 days before MCAO. In the post-treatment, rats received atorvastatin or vehicle for 7 days after MCAO. Measurement of infarct volume, as well as neurological and immunohistochemical assessments, were done 24h and 7 days after reperfusion. KEY FINDINGS: Each atorvastatin-treated group demonstrated significant reductions in infarct and edema volumes compared with the vehicle-treated group 24h after reperfusion. Seven days after reperfusion, infarct volumes in the post-treatment group and continuous-treatment group (but not the pre-treatment group) were significantly smaller than in the vehicle-treated group. Only the continuous-treatment group had significantly improved neurological scores 7 days after reperfusion compared with the vehicle group. Post-treatment and continuous-treatment groups had significantly decreased lipid peroxidation, oxidative DNA damage, microglial activation, expression of tumor necrosis factor-alpha, and neuronal damage in the cortical ischemic boundary area after 7 days of reperfusion. SIGNIFICANCE: These results suggest that continuous oral administration (avoiding withdrawal) with statins after stroke may reduce the extent of post-ischemic brain damage and improve neurological outcome by inhibiting oxidative stress and inflammatory responses.

Effect of repeated allogeneic bone marrow mononuclear cell transplantation on brain injury following transient focal cerebral ischemia in rats.

AIMS: Transplantation of bone marrow mononuclear cells (BMMCs) exerts neuroprotection against cerebral ischemia. We examined the therapeutic timepoint of allogeneic BMMC transplantation in a rat model of focal cerebral ischemia, and determined the effects of repeated transplantation outside the therapeutic window. MAIN METHODS: Male Sprague-Dawley rats were subjected to 90 minute focal cerebral ischemia, followed by intravenous administration of 1 × 10(7) allogeneic BMMCs or vehicle at 0, 3 or 6 h after reperfusion or 2 × 10(7) BMMCs 6 h after reperfusion. Other rats administered 1 × 10(7) BMMCs at 6 h after reperfusion received additional BMMC transplantation or vehicle 9 h after reperfusion. Infarct volumes, neurological deficit scores and immunohistochemistry were evaluated 24 or 72 h after reperfusion. KEY FINDINGS: Infarct volumes at 24 h were significantly decreased in transplantation rats at 0 and 3 h, but not at 6 h, after reperfusion, compared to vehicle-treatment. Even high dose BMMC transplantation at 6h after reperfusion was ineffective. Repeated BMMC transplantation at 6 and 9h after reperfusion reduced infarct volumes and significantly improved neurological deficit scores at 24 and 72 h. Immunohistochemistry showed repeated BMMC transplantation reduced ionized calcium-binding adapter molecule 1, 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine expression at 24 and 72 h after reperfusion. SIGNIFICANCE: Intravenous allogeneic BMMCs were neuroprotective following transient focal cerebral ischemia, and the therapeutic time window of BMMC transplantation was >3 h and <6 h after reperfusion in this model. Repeated transplantation at 6 and 9 h after reperfusion suppressed inflammation and oxidative stress in ischemic brains, resulting in improved neuroprotection.

An unusual cerebral air embolism developing within the posterior circulation territory after a needle lung biopsy.

We herein report the case of a 75-year-old woman with a paradoxical cerebral air embolism (CAE). She developed a bilateral visual disturbance at the time of needle puncture during a computed tomography (CT)-guided percutaneous needle lung biopsy in the face down position. The air density within the descending aorta on chest CT suggested the presence of a cerebral air embolism. Brain MRI demonstrated increased signal intensity in the bilateral occipital lobes on diffusion-weighted images. Usually, CAE occurs predominantly in the right hemisphere for anatomical reasons. The face down position and the anatomical features of the right subclavian artery, which diverges backward from the brachiocephalic artery, might explain such a unique distribution of CAE in this patient.