Noriko Matsumoto

Hyperglycemia independently increases the risk of early death in acute spontaneous intracerebral hemorrhage

BACKGROUND It is unclear whether hyperglycemia on admission in patients with acute intracerebral hemorrhage (ICH) increases the risk of early death. METHODS 100 consecutive patients (median age, 67.8 years) with acute supratentorial ICH within 24 h of onset were prospectively enrolled. Clinical characteristics and plasma glucose were assessed in all patients. ICH volume was measured on admission CT (<24 h) and follow-up CT (<48 h) scans. Patients were divided into two groups: the death group, who died within 14 days of onset, and the survival group. The association between early death and clinical characteristics were investigated by multivariate logistic regression analysis. RESULTS The death group consisted of 11 patients (median age, 77 years), while the survival group consisted of 89 patients (median age, 67 years). The admission plasma glucose level and the ICH volume were higher in the death group than in the survival group (glucose: death, 205 mg/dl vs. survival, 131 mg/dl, p<0.0001; and ICH volume: survival, 13.6+/-15.3 ml vs. death 101.1+/-48.7 ml, p<0.0001). Using receiver operating characteristic (ROC) curve, cut-off values that predicted early death were 150 mg/dl for the glucose level and >20 ml for the initial IVH volume. On multivariate logistic regression analysis, admission plasma glucose level>150 mg/dl (OR 37.5, CI 1.4-992.7, p=0.03) and IVH volume>20 ml (OR 64.6, CI 1.3-3173.5, p=0.04) were independent factors associated with early death. CONCLUSION Admission hyperglycemia may independently increase the risk of early death in acute spontaneous intracerebral hemorrhage.

Brain natriuretic peptide is a marker associated with thrombus in stroke patients with atrial fibrillation

BACKGROUND Patients with atrial fibrillation (AF) and atrial thrombus are at high risk of thromboembolic events. We investigated whether BNP levels can serve as a biological marker of thrombus. METHODS We prospectively enrolled patients with AF within 7days of an ischemic stroke and transient ischemic attack (TIA). We measured BNP levels in all patients while they underwent transesophageal echocardiography (TEE) and then assigned them to groups based on the presence (positive group) or absence (negative group) of left atrial thrombus. Factors associated with atrial thrombus were investigated using multivariate logistic regression analysis. RESULTS Of the 67 (male, n = 40; mean age, 76.5 ± 11.1 years) enrolled patients, 17 (25.4%) had left atrial thrombus. The incidence of hypertension was significantly higher in the positive, than in the negative group (88.2% vs. 58.0%, p = 0.020). The BNP level was also significantly higher in the positive, than in the negative group (median (interquartile range) 189.8 (141.4-473.2) vs. 117.9 (70.3-187.1) pg/ml, p=0.012). The optimal cut-off value, sensitivity, and specificity of BNP levels to distinguish the positive, from the negative group were 140.0 pg/ml, 76.5%, and 62.0%, respectively. Multivariate logistic regression analysis demonstrated that a BNP concentration of>140.0 pg/ml (odds ratio, 5.62; 95% CI, 1.39-22.66, p = 0.015) was an independent factor associated with thrombus. CONCLUSION Levels of BNP can serve as a marker of left atrial thrombus in acute ischemic stroke and TIA in patients with AF.

Neurological deterioration in small vessel disease may be associated with increase of infarct volume

BACKGROUND AND PURPOSE The mechanism of neurological deterioration in small vessel disease is unclear. We examined the relationship between neurological deterioration and change of infarct volume in acute small vessel disease. METHODS We studied consecutive patients with acute supratentorial small vessel disease. Patients were classified into two groups (D: group with deterioration, N: group with no deterioration). We performed serial MRI studies, measured infarct volumes using NIH Image, and calculated the changes in infarct volume (Delta volume) between initial and follow-up diffusion-weighted imaging (DWI). RESULTS Seventy-two patients (44 males, 68+/-11 years of age) were enrolled. Fifteen patients exhibited neurological deterioration (group D) and 57 patients did not (group N). Initial infarct volume was 0.66 cm3 in group D and 0.45 cm3 in group N (p=0.025). Infarct volumes on follow-up DWI were 1.41 cm3 and 0.72 cm3, respectively (p=0.001). The Delta volume in group D was larger than that in group N (0.76 cm3 vs 0.27 cm3, p=0.001). In order to differentiate D from N group, sensitivity specificity analysis yielded a cut-off value of Delta volume of 0.5 cm3 for differentiation of the two groups, which exhibited a sensitivity of 80% and specificity of 84%. Multivariate logistic regression analysis demonstrated that increase in infarct volume of over 0.5 cm3 (odds ratio; 18.0, 95% CI; 1.4 to 270, p=0.027) was independently associated with neurological deterioration in patients with acute small vessel disease. CONCLUSIONS Enlargement of infarct volume may contribute to neurological deterioration in acute small vessel disease.

Early stroke treatment with IV t-PA associated with early recanalization

PURPOSE Time from stroke onset to treatment (OTT) is potentially an important factor affecting subsequent outcome in patients treated with t-PA. The aim of the study was to assess the correlation between OTT and early recanalization rate after IV-t-PA therapy. METHODS Consecutive stroke patients treated with t-PA within 3h of onset were prospectively studied. Patients with major brain artery occlusion on MRA before t-PA infusion were enrolled. The correlation between OTT and the early recanalization rate within 1h after t-PA infusion was determined. RESULTS 102 patients (M1 occlusion, 41 patients; M2, 19; ICA, 31; BA, 8; and PCA, 3) were enrolled. Follow-up MRA within 1h after t-PA infusion showed early recanalization in 42 (41.2%) patients (complete in 13 patients, partial in 29). The early recanalization rate was 53.8% with OTT <or=100 min, 57.1% in 101-110 min, 50.0% in 111-120 min, 63.6% in 121-130 min, 33.3% in 131-140 min, 30.0% in 141-150 min, 36.4% in 151-160 min, 18.2% in 161-170 min, and 32.0% in 171-180 min. OTT was negatively correlated with the early recanalization rate (r=-0.767, P=0.0301). After adjusting the presence of age (>74), ICA occlusion, baseline NIHSS score (<10), and glucose (>150 mg/dl), adjusted OR for early recanalization of OTT <or=130 min against OTT >130-180 min was 2.97 (95% CI 1.27-6.96, P=0.012). CONCLUSION Early recanalization depended on time from stroke onset to IV-t-PA administration. Thus, t-PA should be given to acute stroke patients as soon as possible.

The Presence of a Right-to-Left Shunt Is Associated With Dramatic Improvement After Thrombolytic Therapy in Patients With Acute Ischemic Stroke

Background and Purpose— The efficacy of pharmacological thrombolysis using tissue plasminogen activator depends on the relative fibrin content of the thrombus. We investigated whether patients with stroke with a right-to-left shunt (RLS), whose embolic source was associated with fibrin-rich thrombus formed in the venous system, were more likely to improve dramatically after thrombolytic therapy than those without RLS. Methods— Patients with acute stroke treated with tissue plasminogen activator were assessed prospectively to determine the clinical factors associated with “dramatic improvement” after tissue plasminogen activator administration. “Dramatic improvement” was defined as a ≥10-point reduction in the total National Institutes of Health Stroke Scale score or a total National Institutes of Health Stroke Scale score of 0 or 1 at 7 days. The presence of an RLS was determined using contrast transcranial Doppler within 6 hours of stroke onset. Results— Forty-four patients (26 males; mean age; 73.0±10.7 years; baseline National Institutes of Health Stroke Scale score,13.4±6.6) were enrolled. Twenty-one patients had dramatic improvement (D group). Contrast transcranial Doppler demonstrated an RLS in 17 (35.4%) patients. On multivariate logistic regression analysis using hyperlipidemia, atrial fibrillation, RLS, DWI-ASPECTS (>8), baseline National Institutes of Health Stroke Scale score (<10), and glucose (<120 mg/dL) as variables with a P<0.1 on univariate analysis, RLS (OR, 5.9; CI,1.3 to 27.3; P=0.022) was the only independent factor associated with dramatic improvement. Conclusion— The presence of an RLS on contrast transcranial Doppler was an independent factor associated with dramatic improvement after tissue plasminogen activator administration.

Contrast Transcranial Doppler Can Diagnose Large Patent Foramen Ovale

Background: Contrast transesophageal echocardiography (c-TEE) and contrast transcranial Doppler (c-TCD) are useful diagnostic tools for detecting right-to-left shunts (RLS). However, the diagnostic accuracy of c-TCD for patent foramen ovale (PFO) remains uncertain. We investigated the relationship between the size of PFO determined by c-TEE and c-TCD findings and assessed the detectable rate of RLS by c-TCD. Methods: We assessed RLS three times using simultaneous c-TCD and c-TEE in 107 patients (321 examinations). We classified all of ultrasound examinations into three groups by size according to microbubbles on c-TEE, such as no PFO (0 microbubble), small PFO (1–29 microbubbles) and large PFO (≥30 microbubbles). We also calculated the number of microembolic signals (MES) on c-TCD and evaluated the association between PFO size on c-TEE and MES count on c-TCD. Results: In the present study, c-TEE detected RLS in 105 (33%; small PFO, n = 78; large PFO, n = 27), and c-TCD detected RLS in 49 (15%) of 321 examinations. Among 78 examinations with small PFO, MES were found in only 19 (24%) on c-TCD. In contrast, of all 27 examinations with large PFO, MES were found on c-TCD. Also, c-TCD were able to detect MES in 3 of 216 examinations among the no-PFO group. When ≥2 MES on c-TCD was established as the cutoff to predict large PFO on c-TEE, the sensitivity, specificity and accuracy were 96.3, 96.8, and 96.9%, respectively. Conclusion: When two or more MES were determined by c-TCD, large PFO could be accurately diagnosed.

Recanalization between 1 and 24 hours after t-PA therapy is a strong predictor of cerebral hemorrhage in acute ischemic stroke patients

BACKGROUND AND PURPOSE Intravenous administration of tissue plasminogen activator (t-PA) can improve clinical outcomes in patients with acute ischemic stroke. The most important complication of t-PA therapy is intracerebral hemorrhage (ICH). The aim of this study was to use serial MRI studies to identify independent predictors of symptomatic and asymptomatic ICH after t-PA therapy. METHODS Consecutive anterior-circulation ischemic stroke patients treated with t-PA within 3 h of stroke onset were studied prospectively. To identify the presence of recanalization in the occluded arteries and the presence of ICH, MRI, including diffusion weighted imaging (DWI), T2*, and magnetic resonance angiography (MRA), was performed before and 1 h, 24 h, and 5-7 days after t-PA thrombolysis. The independent predictors of ICH were determined using multivariate logistic regression analysis. RESULTS 41 patients (21 males, 20 females; mean age, 73.2+/-10.7 years) were enrolled, and 19 ICHs (1 symptomatic, 18 asymptomatic) were observed on T2*. The initial MRA demonstrated occluded brain arteries in 31 patients (75.6%), of which follow-up MRA at 1 h, 24 h, and 5-7 days after t-PA therapy revealed recanalization in 48.4%, 80.0%, and 90.0% of patients, respectively. The frequency of recanalization within 1 h after t-PA therapy did not differ between ICH and No-ICH groups, but the ICH group had more frequent recanalization between 1 h and 24 h after t-PA than the No-ICH group (50.0% vs. 4.5%, P=0.001). The ICH group had arterial fibrillation (AF) more frequently than the No-ICH group (78.9% vs. 27.3%, P=0.001). Compared to the No-ICH group, the NIHSS score was higher (16.4+/-5.7 vs. 11.5+/-6.5, P=0.011) and the ASPECTS-DWI value (a normal DWI has an ASPECTS-DWI value of 11 points) was lower (7.3+/-2.4 vs. 8.9+/-1.9, P=0.019) in the ICH group. Multivariate logistic regression analysis demonstrated that the presence of recanalization between 1 and 24 h after the end of t-PA infusion (OR: 20.2; CI: 1.0-340.9; P=0.037) was the only independent predictor of ICH. CONCLUSION Recanalization of occluded arteries between 1 and 24 h but not within 1 h after t-PA infusion should be independently associated with symptomatic and asymptomatic ICH after t-PA therapy.

Chronic kidney disease is an independent predictor of adverse clinical outcomes in patients with recent small subcortical infarcts.

Background: Chronic kidney disease (CKD) is associated with cerebral small vessel diseases (SVD) and predicts stroke, cardiovascular events and mortality. However, its association with recent small subcortical infarcts (RSSI), a novel subtype of cerebral SVD, has not yet been established in stroke patients. The aim of this longitudinal study was to clarify whether CKD can predict clinical outcome in patients with RSSI. Methods: We enrolled patients with first-ever RSSI (formerly categorized as acute lacunar stroke). CKD was defined as an estimated glomerular filtration rate of <60 ml/min/1.73 m2 on admission. The patients were divided into two groups according to the presence or absence of CKD. The endpoints were recurrent stroke, cardiovascular events or all-cause mortality. The patients were followed up at 3, 6 and 12 months after stroke onset and yearly thereafter. Event-free survival analysis was undertaken using Kaplan-Meier plots and the log-rank test. Coxs proportional-hazards analysis was conducted regarding age, sex and the presence of any cerebral SVD. Results: A total of 152 patients (66% males; mean age: 67.6 years) were consecutively enrolled, and 44 (29%) had CKD. During the follow-up period (median: 3 years; interquartile range: 1-4), 27 patients (18%) reached endpoints. The numbers of patients per endpoint were as follows: all-cause mortality 14, ischemic stroke 9, hemorrhagic stroke 2 and aortic dissection 2. Patients with CKD were significantly older (77 vs. 64 years; p < 0.001), had higher serum creatinine (0.96 vs. 0.65 mg/dl; p < 0.001), higher brain natriuretic peptide (51.1 vs. 18.5 pg/ml; p < 0.001) and a higher National Institutes of Health Stroke Scale score on admission (3 vs. 2; p < 0.001), and were less likely to have modified Rankin Scale scores of 0-2 after stroke onset (52 vs. 77%; p = 0.003). Patients with white matter hyperintensity [odds ratio (OR) 3.0; 95% confidence interval (CI): 1.5-6.2; p = 0.003] and those with microbleeds (OR 2.5; 95% CI: 1.2-5.1; p = 0.015) had more pronounced CKD than the remaining patients. A Kaplan-Meier curve analysis showed that patients with CKD had a less favorable outcome than those without CKD (p < 0.001). The multivariate Cox proportional-hazards analysis revealed that CKD was associated with recurrent stroke, cardiovascular events or all-cause mortality (hazard ratio 2.22; 95% CI: 1.12-4.25; p = 0.02). Conclusions: CKD was found to be independently associated with recurrent stroke, cardiovascular events or all-cause mortality in patients with RSSI.

Early neurological deterioration represents recurrent attack in acute small non-lacunar stroke.

The aim of this study was to identify the frequency and possible pathogenic mechanisms of early neurological deterioration in patients with acute small non-lacunar infarction. We studied 46 patients (35 men, 11 women; age, 70.3+/-10.4 years) with acute small non-lacunar infarction. Small non-lacunar infarction was diagnosed using diffusion-weighted magnetic resonance imaging (DWI) as being <15 mm in diameter and located in the cortex and centrum ovale in the middle cerebral artery territory. The patients were divided into two groups; Group D (n=6) had neurological deterioration within 7 days after symptom onset, while Group N (n=40) did not have any neurological deterioration. In Group D, the interval from symptom onset to clinical deterioration was 3.3+/-1.5 days (range 2-6 days). Blood pressure on admission was higher in Group D than in Group N (p<0.05). In Group D, four of these five patients with follow-up DWI had new acute small ischemic lesions in addition to the initial lesions, indicating recurrent attacks of brain infarction. Neurological deterioration occurred within 7 days after symptom onset in 13% of patients. Neurological deterioration was frequently caused by recurrent infarction detected by DWI.

Enhanced carotid plaque on contrast-enhanced ultrasound is associated with plaque instability and rupture.

Background: Ischemic stroke is one of causes of atherosclerotic diseases, and is closely associated with vulnerable plaque at the origin of the internal carotid artery. Several studies have shown that neovascularization in atheromatous plaque serves as a reliable maker of plaque vulnerability.Contrast-enhanced ultrasound (CEUS) can demonstrate the presence of carotid intraplaque neovascularization. The aim of the present study was to investigate the histopathologic findings of enhanced carotid plaque on CEUS. Methods: We studied consecutive 18 patients (16 men, mean age 69.4 ± 6.7 years) who underwent carotid endarterectomy. Enhanced plaque was classified into two subgroups: a spotty pattern as moving bright spots within plaque (Figure 1A, Panel A); and a linear pattern, where enhanced lesions appeared as a line from intima into plaque (Figure 1B, Panel A). Sonazoid (Daiich-Sankyo, Tokyo, Japan), perflurobutane microbubbles, was used as the contrast agent. A bolus intravenous injection of Sonazoid (0.015 mL/kg body weight (0.12 μ L perflurobutane microbubble /kg body weight)) was performed via the peripheral venous line followed by a flush with 10 mL of normal saline. We investigated the association between enhanced plaque on CEUS and histopathologic findings. Results: CEUS revealed enhanced plaque in 11 (61.1%) of 18 patients. Only a spotty pattern (spotty subgroup) was observed in 5 patients, whereas both a spotty and linear pattern (linear subgroup) was observed in 6. The amount of neovascularization was larger in enhanced than in non-enhanced plaque (6.79 ± 5.17/2.5 mm 2 vs. 1.12 ± 0.90/2.5 mm 2 , P=0.001). Furthermore, the enhanced group had more macrophage aggregation (7.76 ± 3.70% vs. 4.23 ± 1.63%, P=0.030) and intraplaque hemorrhage (18.84 ± 14.88% vs. 5.52 ± 9.68%, P=0.013) compared with the non-enhanced group. Thin fibrous cap ( Conclusions: Enhanced plaque on CEUS indicates vulnerable plaque. A linear pattern of enhanced plaque indicates plaque rupture. Enhanced plaque on CEUS should become a new surrogate marker of vulnerable carotid plaque.