Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants: The PASTA Registry - Study Design and Characteristics.

OBJECTIVES: The management of atrial fibrillation and deep venous thrombosis has evolved with the development of direct oral anticoagulants (DOAC), and oral anticoagulant (OAC) might influence the development or clinical course in both ischemic and hemorrhagic stroke. However, detailed data on the differences between the effects of the prior prescription of warfarin and DOAC on the clinical characteristics, neuroradiologic findings, and outcome of stroke are limited. DESIGN: The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke (ischemic stroke, transient ischemic attack, and intracerebral hemorrhage) patients receiving OAC in Japan. This study is designed to collect data on clinical background characteristics, drug adherence, drug dosage, neurological severity at admission and discharge, infarct or hematoma size, acute therapy including recanalization therapy or reverse drug therapy, and timing of OAC re-initiation. Patient enrollment started in April 2016 and the target patient number is 1000 patients. CONCLUSIONS: The PASTA prospective registry should identify the status of stroke patients taking OAC in the current clinical practice in Japan.

Decrease of Hyperintense Vessels on Fluid-Attenuated Inversion Recovery Predicts Good Outcome in t-PA Patients.

BACKGROUND AND PURPOSE: Hyperintense vessels (HV) detected on fluid-attenuated inversion recovery (FLAIR) in patients with acute ischemic stroke (AIS) indicate cerebral hypoperfusion. However, the clinical meaning of changes in HV is yet to be clarified. Here, we investigated serial changes to HV in patients with AIS who received tissue plasminogen activator (t-PA) therapy. METHODS: We studied t-PA patients presenting with HV on FLAIR in the middle cerebral artery territory. Patients underwent brain MRI 1 h before and after t-PA infusion. HV scores (range 1-7) were evaluated according to Alberta Stroke Program Early Computed Tomography Score territories, and then by subtracting HV scores at 1 h after t-PA infusion from those on admission, with a result of >1 defined as decrease in HV score (DHV). Patients were divided into 2 groups based on the presence or absence of DHV. Multivariate logistic regression analysis was conducted to identify variables independently associated with good outcome (modified Rankin Scale score at 90 days after stroke onset of 0-1). RESULTS: A total of 118 consecutive patients were enrolled (73 men; mean age 76 ± 9.7; median initial National Institutes of Health Stroke Scale (NIHSS) 13; median initial HV score 5), of whom 52 (44%) had DHV. Patients with DHV showed a significantly lower NIHSS time course (p < 0.001) and significantly smaller infarct volume time course (p < 0.001) compared to those without DHV. Multivariate analysis showed that DHV was independently associated with good outcome (OR 3.89; 95% CI 1.55-9.77; p < 0.01). The sensitivity and specificity of DHV for good outcome were 70 and 68%, respectively. CONCLUSION: A DHV on FLAIR predicts good outcome in patients receiving t-PA.

Post Stroke Dysglycemia and Acute Infarct Volume Growth: A Study Using Continuous Glucose Monitoring.

BACKGROUND: The aim of the present study was to clarify the effect of glucose profiles after stroke, which was assessed by a continuous glucose monitoring (CGM) device. METHODS: Acute ischemic stroke patients within 24 h of onset were prospectively studied. CGM was performed for 72 h after admission. CGM parameters were evaluated as follows: (1) mean glucose level, (2) area under the curve (AUC) for glucose level >140 mg/dl and (3) SD of the glucose level. Infarct volume was measured at admission and 24 and 72 h after admission using diffusion-weighted imaging. CGM data and infarct volume growth were compared at 24 and 72 h. RESULTS: Seventy-eight patients were enrolled in the present study. Spearman's rank correlation coefficients showed that both the mean glucose level (r = 0.433, p < 0.001 for 24 h; r = 0.308, p = 0.006 for 72 h) and AUC >140 mg/dl (r = 0.417, p < 0.001 for 24 h; r = 0.277, p = 0.014 for 72 h) were significantly correlated with acute infarct volume growth. The SD of the glucose level was associated with infarct volume growth at 24 h (r = 0.303, p = 0.007), but not 72 h (r = 0.195, p = 0.088). CONCLUSION: Post-stroke hyperglycemia was associated with infarct volume growth during the acute phase of ischemic stroke.

B-type natriuretic peptides help in cardioembolic stroke diagnosis: pooled data meta-analysis.

BACKGROUND AND PURPOSE: Determining the underlying cause of stroke is important to optimize secondary prevention treatment. Increased blood levels of natriuretic peptides (B-type natriuretic peptide/N-terminal pro-BNP [BNP/NT-proBNP]) have been repeatedly associated with cardioembolic stroke. Here, we evaluate their clinical value as pathogenic biomarkers for stroke through a literature systematic review and individual participants' data meta-analysis. METHODS: We searched publications in PubMed database until November 2013 that compared BNP and NT-proBNP circulating levels among stroke causes. Standardized individual participants' data were collected to estimate predictive values of BNP/NT-proBNP for cardioembolic stroke. Dichotomized BNP/NT-proBNP levels were included in logistic regression models together with clinical variables to assess the sensitivity and specificity to identify cardioembolic strokes and the additional value of biomarkers using area under the curve and integrated discrimination improvement index. RESULTS: From 23 selected articles, we collected information of 2834 patients with a defined cause. BNP/NT-proBNP levels were significantly elevated in cardioembolic stroke until 72 hours from symptoms onset. Predictive models showed a sensitivity >90% and specificity >80% when BNP/NT-proBNP were added considering the lowest and the highest quartile, respectively. Both peptides also increased significantly the area under the curve and integrated discrimination improvement index compared with clinical models. Sensitivity, specificity, and precision of the models were validated in 197 patients with initially undetermined stroke with final pathogenic diagnosis after ancillary follow-up. CONCLUSIONS: Natriuretic peptides are strongly increased in cardioembolic strokes. Future multicentre prospective studies comparing BNP and NT-proBNP might aid in finding the optimal biomarker, the best time point, and the optimal cutoff points for cardioembolic stroke identification.

Risk of intracerebral hemorrhage after thrombolysis in patients with asymptomatic hemorrhage on T2*.

BACKGROUND: Intravenous thrombolysis using the tissue-type plasminogen activator (t-PA) is contraindicated for patients with a history of intracerebral hemorrhage (ICH). T2*-weighted magnetic resonance imaging (MRI) is able to detect asymptomatic ICH. If there is an association between asymptomatic ICH on T2* before t-PA therapy and ICH after t-PA therapy, we may be able to take preventive measures before starting t-PA therapy in patients with MRI-proven hemorrhage. The aim of the present study was to investigate whether asymptomatic ICH seen on T2* increases the risk of new ICH after t-PA therapy. METHODS: Patients who had consecutive stroke treated with t-PA between October 2005 and November 2013 were enrolled. A hypointense T2* signal with a diameter >5 mm was defined as asymptomatic ICH before t-PA therapy. The presence of new ICH at 24 h after t-PA therapy was assessed using T2*. Symptomatic ICH (sICH) was defined as new ICH combined with an increase in the National Institutes of Health Stroke Scale score ≥4. At 3 months after onset, good and poor outcomes were defined as modified Rankin Scale (mRS) scores of 0-1 and 4-6, respectively. RESULTS: Of 300 patients (age 77 [68-83] years; 173 [58%] males), 25 (8%) had an asymptomatic ICH on T2* before t-PA therapy. Eleven (45%) patients showed an isolated asymptomatic ICH. Three (12%) patients had a round hypointense lesion similar to microbleeds. Nine (36%) patients had a hemorrhagic transformation within a prior infarcted area. Multiple asymptomatic ICHs were seen in 2 (8%) patients. The rates of good and poor outcomes at 3 months were 24 and 59% of patients with asymptomatic ICH and 38 and 41% of patients without asymptomatic ICH (p = 0.300 and 0.202, respectively). At 24 h after t-PA therapy, 11 (44%) of the 25 patients with asymptomatic ICH before t-PA therapy and 87 (32%) of 275 without asymptomatic ICH had new ICH (p = 0.265). Only 1 (4%) of 25 patients with asymptomatic ICH before t-PA therapy and 6 (2%) of 275 without asymptomatic ICH had sICH within 24 h (p = 0.460). On multivariate logistic regression analysis, neither new ICH (odds, 1.19; 95% CI, 0.40-3.54, p = 0.753) nor sICH (odds, 0.95; 95% CI, 0.08-11.90, p = 0.970) was related to asymptomatic ICH on T2* before t-PA therapy. CONCLUSION: The presence of T2* hypointensity as a marker of asymptomatic ICH may not be associated with new ICH and sICH after t-PA therapy.

Brain natriuretic peptide upon admission as a biological marker of short-term mortality after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: The purpose of the present study was to test the hypothesis that plasma brain natriuretic peptide (BNP) is associated with short-term mortality after intracerebral hemorrhage (ICH). METHODS: We prospectively enrolled 271 patients (median age 72 years; 109 females) who were admitted within 24 h of ICH onset between April 2007 and July 2011 and in whom plasma BNP levels were measured upon admission. The patients were assigned to two groups according to survival within 1 month of ICH. Factors associated with mortality were determined by multivariate logistic regression analysis. RESULTS: Within 1 month of ICH, 48 (17.7%) of the 271 enrolled patients died. The median (interquartile range) level of plasma BNP was significantly higher in the group of non-survivors than in the group of survivors [102.5 (48.7-205.0) vs. 32.4 (17.3-85.0) pg/ml; p < 0.001]. A cutoff BNP level of 60.0 pg/ml could predict death within 1 month of ICH. Multivariate logistic regression analysis showed that a plasma BNP of >60.0 pg/ml (OR 4.7; 95% CI 1.43-15.63; p = 0.011) was independently associated with mortality within 1 month after ICH. CONCLUSIONS: A high BNP level upon admission is associated with mortality within 1 month after ICH.

Plasma brain natriuretic Peptide as a predictive marker of early recurrent stroke in cardioembolic stroke patients.

BACKGROUND: Whether brain natriuretic peptide (BNP) levels are associated with early recurrent stroke in cardioembolic stroke patients was investigated. METHODS: From January 2010 to March 2014, consecutive patients within 24 hours of onset of cardioembolic stroke were prospectively enrolled, and admission plasma BNP levels were measured. Recurrent stroke was identified as the occurrence of additional neurologic deficits and the appearance of a new infarct on neuroimaging. Patients were divided into 2 groups: the recurrence group and the nonrecurrence group. Factors associated with stroke recurrence were investigated by multiple logistic regression analysis. RESULTS: A total of 348 patients were included; 17 patients (5%) had recurrent stroke during hospitalization. The median interval from stroke onset to recurrent stroke was 4 days (range, 0-30). BNP levels were significantly higher in the recurrence group than in the nonrecurrence group (304.1 vs. 206.5 pg/mL, P = .029). The optimal cutoff level, sensitivity, and specificity of BNP levels to distinguish the recurrence group from the nonrecurrence group were 255.0 pg/mL, 76%, and 60%, respectively. On multivariate analysis after adjustment for confounders, plasma BNP ≥ 255.0 pg/mL (odds ratio, 5.21; 95% confidence interval, 1.63-16.72; P = .005) was independently associated with recurrent stroke during hospitalization in cardioembolic stroke patients. CONCLUSIONS: Plasma BNP could be a useful marker for predicting early recurrent stroke during hospitalization in cardioembolic stroke patients.

The role of small vessel disease in re-exacerbation of stroke symptoms within 24 hours after tissue plasminogen activator infusion.

BACKGROUND: The purpose of this study was to examine the frequency and characteristics of re-exacerbation of stroke symptoms within 24 hours after tissue plasminogen activator (t-PA) infusion. METHODS: We studied consecutive stroke patients treated with t-PA within 3 hours of onset of symptoms admitted between October 2005 and March 2010. We divided patients into 4 groups: improvement (IM; improvement in National Institutes of Health Stroke Scale [NIHSS] ≥4 points), unchanged (UN; no change or decline in NIHSS <4 points), exacerbation (EX; decline in NIHSS ≥4 points), and re-exacerbation (RE-EX; decline of NIHSS ≥4 points accompanied by re-exacerbation of neurologic symptoms in NIHSS ≥4 points). We compared clinical characteristics among the 4 groups. RESULTS: Two hundred twenty-two patients (135 men; median age 76 years) were enrolled. Sixteen of the 222 (7%) were in the RE-EX group. Small vessel disease (SVD), hemorrhagic cerebral infarction, and reocclusion were significantly more common among patients in the RE-EX group. SVD, hemorrhagic cerebral infarction, and reocclusion occurred in 44%, 25%, and 13% of patients in the RE-EX group, in 9%, 22%, and 0% of patients in the EX group, in 5%, 6%, and 0% of patients in the IM group, and in 17%, 14%, and 1% of patients in the UN group, respectively (P < .001, P = .041, and P < .001). Multivariate logistic regression analysis revealed that SVD was the only independent factor associated with re-exacerbation within 24 hours after t-PA infusion (odds ratio 3.52; 95% confidence interval [CI] 1.19-10.40; P = .023). CONCLUSIONS: Seven percent of patients re-exacerbated within 24 hours after intravenous infusion of t-PA. Re-exacerbation within 24 hours after t-PA infusion was strongly associated with SVD.

Usefulness of magnetic resonance imaging in differentiation between status epilepticus and acute ischemic stroke.

BACKGROUND: Status epilepticus, characterized by the temporal neurological deficits, often mimics acute ischemic stroke. We investigated the usefulness of magnetic resonance imaging for differentiation of status epilepticus from acute ischemic stroke. METHODS: A retrospective case series of patients with status epilepticus who underwent brain magnetic resonance imaging. For comparative analysis, a series of patients with acute ischemic stroke caused by unilateral middle cerebral artery occlusion was used. RESULTS: Ten patients (4 females and 6 males) with status epilepticus who underwent brain magnetic resonance imaging were included. The median age at diagnosis was 82 years (age range, 70-90 years). In all ten patients, hyperintensities in diffusion-weighted imaging with decreased apparent diffusion coefficient values, decreased venous intensity in susceptibility-weighted imaging, and hyperperfusion in arterial spin labeling perfusion were detected in the cortex of the affected side. Four patients showed an additional diffusion restriction in the thalamus. The apparent diffusion coefficient value of the lesional area was 13.1% less than the contralateral, which was less than one-third as acute ischemic stroke. Status epilepticus patients showed no change in medullary venous intensity of the affected area in susceptibility-weighted imaging, whereas acute ischemic stroke patients showed increased cortical and medullary venous intensity in affected hemisphere. Seven of eight patients with status epilepticus who underwent magnetic resonance angiography showed dilation of the cerebral arteries in the ipsilateral side. CONCLUSIONS: The combined use of diffusion-weighted imaging, susceptibility-weighted imaging, and arterial spin labeling perfusion may help accurate and prompt diagnosis of status epilepticus.

DWI-ASPECTS as a predictor of dramatic recovery after intravenous recombinant tissue plasminogen activator administration in patients with middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: In patients with middle cerebral artery trunk occlusion we investigated whether the diffusion-weighted imaging- the Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) predicts short-term neurological recovery after intravenous recombinant tissue plasminogen activator administration, and investigated how DWI-ASPECTS relates to clinical outcome. METHODS: Dramatic recovery was defined as a ≥ 10-point reduction or a total National Institutes of Health Stroke Scale score of 0 to 1 at 24 hours and 7 days. Early recanalization was defined as recanalization within 1 hours after intravenous recombinant tissue plasminogen activator. Favorable outcome at 3 months was defined as a modified Rankin Scale score of 0 to 2. RESULTS: Sixty-six patients (median age [interquartile], 79 [70-85] years, male; 34 [52%]) were enrolled. DWI-ASPECTS was 6 (5-9). Dramatic recovery was seen in 16 (24%) and 26 (39%) patients at 24 hours and on day 7, respectively. Early recanalization occurred in 22 (33%) patients. DWI-ASPECTS ≥ 7 was an independent predictor of dramatic recovery at 24 hours (odds ratio, 100.85; 95% confidence interval, 4.29-2371.40; P=0.004) and 7 days (odds ratio, 14.15; 95% confidence interval, 2.21-90.48; P=0.005). Although the favorable outcome rate was not significantly different between patients with DWI-ASPECTS ≥ 7 with and without early recanalization (60% versus 31%; P=0.228), it was statistically more frequent in patients with DWI-ASPECTS <7 with early recanalization than those without early recanalization (38% versus 0%; P=0.017). CONCLUSIONS: DWI-ASPECTS predicted short-term recovery in patients with middle cerebral artery trunk occlusion receiving intravenous recombinant tissue plasminogen activator. In patients with lower DWI-ASPECTS, there may still be benefit from early recanalization.

New appearance of extraischemic microbleeds on T2*-weighted magnetic resonance imaging 24 hours after tissue-type plasminogen activator administration.

BACKGROUND AND PURPOSE: It is unknown whether new-extraischemic microbleeds (new-EMBs) develop rapidly after tissue-type plasminogen activator (tPA) infusion. We hypothesized that new-EMBs may develop rapidly after tPA infusion using T2*-weighted MRI (T2*) and investigated the frequency and clinical factors associated with new-EMBs. METHODS: Patients with acute stroke within 3 hours of onset who were treated with tissue-type plasminogen activator (tPA) were studied prospectively. T2* was performed before and 24 hours after tPA therapy. Independent clinical factors associated with new-EMBs development were examined using multivariate logistic regression analysis. RESULTS: A total of 224 patients (121 men; mean age, 76.2±10.6 years) were enrolled in the present study. MBs before tPA infusion were observed in 72 (32.1%) patients. Within 24 hours after tPA infusion, 6 (2.7%) patients had symptomatic intracranial hemorrhage (extraischemic [n=4], and hemorrhagic transformation [n=2]). Follow-up T2* revealed asymptomatic new-EMBs in 11 (4.9%) patients and hemorrhagic transformation in the infarcted area in 65 (29.0%). The total and mean number of new-EMBs were 23 and 1.6±1.3, respectively. Patients with new-EMBs more frequently had symptomatic extraischemic hemorrhage than those without new-EMBs (27.3% [3/11] versus 0.5% [1/213]; P=0.0003). However, the frequency of hemorrhagic transformation was not different between patients with and without new-EMBs (27.3% versus 29.1%; P=0.9999). Multivariate logistic regression demonstrated that the presence of MBs before tPA infusion was the only independent factor associated with new-EMBs (odds ratio, 10.6; 95% confidence interval, 20.68-54.279; P=0.0046). CONCLUSIONS: New-EMBs occurred rapidly after tPA infusion in 4.9% of patients. The presence of MBs before tPA therapy was associated with new-EMBs. Patients with new-EMBs are likely to have symptomatic extraischemic hemorrhage.

Maintenance hemodialysis independently increases the risk of early death after acute intracerebral hemorrhage.

BACKGROUND: It is unknown whether the clinical features and outcomes of intracerebral hemorrhage (ICH) patients who undergo maintenance hemodialysis (HD) at the time of ICH are similar to those of general ICH patients. METHODS: We retrospectively examined the medical records of ICH patients admitted to the Stroke Center of Kawasaki Medical School Hospital within 7 days of ICH onset between April 2004 and June 2011. Patients were classed as HD or non-HD, and clinical characteristics were compared between the two groups. ICH volume was measured on admission CT and follow-up CT scan (< 24 h after admission). Hematoma enlargement was defined as a hematoma that increased by more than 33% of its initial volume. Early death was defined as all-cause death within 14 days of ICH onset. The factors associated with early death were determined using multivariate logistic regression analysis. RESULTS: Five hundred and seven patients (320 males; 69.0 years old, interquartile range 59.0-79.0) were enrolled in the study. Thirty-six (7.2%) were receiving maintenance HD at the time of ICH and formed the HD group, and the remaining 471 patients formed the non-HD group. Use of antithrombotic agents prior to ICH was more common in the HD group than in the non-HD group (41.7 vs. 21.9%; p = 0.012). Brainstem (30.6 vs. 11.3%; p = 0.003) and lobar (19.4 vs. 6.6%; p = 0.013) hematoma locations were more common in the HD group than in the non-HD group. Enlargement of ICH volume was more common in the HD group than in the non-HD group (25.8 vs. 10.2%; p = 0.015). Early death was more common in the HD group than in the non-HD group (33.3 vs. 9.3%; p < 0.001). On the multivariate logistic regression analysis adjusted for age, sex and renal dysfunction, National Institutes of Health Stroke Scale score > 20 [odds ratio (OR) 27.40, 95% confidence interval (CI) 9.69-77.44; p < 0.001], ICH volume > 30 ml (OR 9.53, 95% CI 3.82-23.77; p < 0.001), HD (OR 6.42, 95% CI 1.39-29.76; p = 0.017), the use of antithrombotic agents (OR 3.04, 95% CI 1.22-7.56; p = 0.017) and glucose > 150 mg/dl (OR 2.51, 95% CI 1.01-6.26; p = 0.047) were independent factors associated with early death. CONCLUSION: Maintenance HD is independently associated with early death in ICH patients.

Brain natriuretic peptide on admission as a biological marker of long-term mortality in ischemic stroke survivors.

BACKGROUND AND PURPOSE: We investigated whether brain natriuretic peptide (BNP) can serve as a biological marker of long-term mortality in ischemic stroke survivors. METHODS: Consecutive patients with ischemic stroke within 24 h of onset from April 2007 to December 2010 were prospectively enrolled, and admission plasma BNP levels were measured. Survivors were followed up until 1 year after stroke onset. Patients were divided into two groups: the deceased group and the surviving group. The factors associated with long-term mortality were investigated by multiple logistic regression analysis. RESULTS: A total of 736 patients who were alive at hospital discharge were included; 130 (17.7%) patients died. On multivariate analysis, age>75 years (odds ratio, OR, 2.83; 95% CI, 1.74-4.60, p=0.0001), dialysis-dependent chronic renal failure (OR, 5.99; 95% CI, 2.18-16.47, p=0.0005), modified Rankin Scale score>3 at discharge (OR, 4.41; 95% CI, 2.76-7.05, p<0.0001), and plasma BNP>100.0 pg/ml (OR, 3.94; 95% CI, 2.31-6.73, p<0.0001) were found to be independently associated with long-term mortality. We developed a risk score from 4 variables (each variable: 1 point, total score: 0-4 points). The mortality rates were 2% with a score of 0, 9% with a score of 1, 27% with a score of 2 and 50% with a score≥3. CONCLUSIONS: The risk score, composed of clinical parameters and BNP, may predict long-term mortality in ischemic stroke survivors.

Brain natriuretic peptide as a predictor of cardioembolism in acute ischemic stroke patients: brain natriuretic peptide stroke prospective study.

BACKGROUND AND PURPOSE: Our previous retrospective study demonstrated that a brain natriuretic peptide (BNP) level of >140 pg/ml on admission was useful to distinguish cardioembolism (CE) from non-CE. The aim of the present study was to prospectively investigate the utility of this predefined threshold. METHOD: Two hundred and twenty-one consecutive patients were prospectively enrolled. On admission, the BNP levels of the patients were measured and classified according to low BNP (≤140.0 pg/ml) or high BNP (>140.0 pg/ml) levels. Final diagnosis of stroke subtype on discharge was made using the TOAST criteria. Measured parameters included the sensitivity, specificity, positive predictive value, and negative predictive value for CE in the high BNP group. RESULTS: There were 81 patients in the high BNP group and 140 patients in the low BNP group. A total of 76 (34.4%) patients were diagnosed with CE, including 59 (72.8%) patients in the high BNP group and 17 (12.1%) patients in the low BNP group (p < 0.001). A BNP level >140.0 pg/ml corresponded to a sensitivity of 77.6%, specificity of 84.8%, positive predictive value of 72.8%, and negative predictive value of 87.9% for a diagnosis of CE. CONCLUSION: A BNP level of >140.0 pg/ml on admission in patients with acute ischemic stroke is a strong biochemical predictor for CE.

A small pontine infarct on DWI as a lesion responsible for wall-eyed bilateral internuclear ophthalmoplegia syndrome.

A 64-year-old man presented with alternating exotropia and bilateral medial longitudinal fasciculus (MLF) syndrome known as wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome. Diffusion-weighted imaging showed a small localized lesion in the median dorsal pons, and high-resolution T2-weighted imaging revealed slight left deviation of the lesion. A small penetrating artery was assumed to be occluded at the level of the MLF decussation. The median dorsal pons appears to be a location for the lesions causing WEBINO syndrome.

Prior direct oral anticoagulant dosage and outcomes in patients with acute ischemic stroke and non-valvular atrial fibrillation: A sub-analysis of PASTA registry study.

BACKGROUND AND PURPOSE: Prescribing under-dose direct oral anticoagulants (DOACs) for non-valvular atrial fibrillation (NVAF) is alerted to increase cardiovascular events or death. However, the association between dose selection of DOACs and the clinical course remains unclear. This study aimed to propose a novel criterion for selecting the DOAC dose and investigate clinical characteristics of ischemic stroke (IS) under this criterion. METHODS: We assessed the pooled prospective multicenter registry data of stroke patients taking anticoagulant agents, including IS patients with NVAF and prior DOAC usage. The recommended dose according to the reduction criteria of each DOAC and the selected dose were identified for each patient, and patients were categorized into four groups: no alternative low-dose, selecting low-dose appropriately with all DOACs applicable for reduction criteria; selected low-dose, selecting low-dose appropriately or inappropriately despite at least one DOAC inapplicable for reduction criteria; selected standard-dose, appropriate standard-dose use; and absolute over-dose, inappropriate standard-dose regardless of criteria. We investigated the effects of dose selection of DOACs on short-term poor functional outcomes. RESULTS: 322 patients were included in the analysis. The prevalence of no alternative low-dose, selected low-dose, selected standard-dose, and absolute over-dose was 74 (23%), 144 (45%), 89 (27%), and 15 (5%), respectively. Multivariable analysis found that the selected low-dose group showed significantly poorer functional outcomes than the selected standard-dose group only in patients without renal dysfunction (OR, 2.60; 95% CI, 1.17-6.00; P = 0.0186). CONCLUSIONS: Selecting a low dose DOAC might be associated with poor functional outcomes in patients without renal dysfunction.

Characteristics of Ischemic Versus Hemorrhagic Stroke in Patients Receiving Oral Anticoagulants: Results of the PASTA Study.

Objective Limited data exist regarding the comparative detailed clinical characteristics of patients with ischemic stroke (IS)/transient ischemic attack (TIA) and intracerebral hemorrhage (ICH) receiving oral anticoagulants (OACs). Methods The prospective analysis of stroke patients taking oral anticoagulants (PASTA) registry, a multicenter registry of 1,043 stroke patients receiving OACs [vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulant (NOACs)] across 25 medical institutions throughout Japan, was used. Univariate and multivariable analyses were used to analyze differences in clinical characteristics between IS/TIA and ICH patients with atrial fibrillation (AF) who were registered in the PASTA registry. Results There was no significant differences in cardiovascular risk factors, such as hypertension, diabetes mellitus, dyslipidemia, smoking, or alcohol consumption (all p>0.05), between IS/TIA and ICH among both NOAC and VKA users. Cerebral microbleeds (CMBs) [odds ratio (OR), 4.77; p<0.0001] were independently associated with ICH, and high brain natriuretic peptide/N-terminal pro B-type natriuretic peptide levels (OR, 1.89; p=0.0390) were independently associated with IS/TIA among NOAC users. A history of ICH (OR, 13.59; p=0.0279) and the high prothrombin time-international normalized ratio (PT-INR) (OR, 1.17; p<0.0001) were independently associated with ICH, and a history of IS/TIA (OR, 3.37; 95% CI, 1.34-8.49; p=0.0101) and high D-dimer levels (OR, 2.47; 95% CI, 1.05-5.82; p=0.0377) were independently associated with IS/TIA among VKA users. Conclusion The presence of CMBs, a history of stroke, natriuretic peptide and D-dimer levels, and PT-INR may be useful for risk stratification of either IS/TIA or ICH development in patients with AF receiving OACs.

Clinical and MRI predictors of no early recanalization within 1 hour after tissue-type plasminogen activator administration.

BACKGROUND AND PURPOSE: The aim of the present study was to investigate independent clinical and MRI factors associated with no early recanalization within 1 hour after tissue-type plasminogen activator (tPA) administration. METHODS: Patients with acute stroke within 3 hours of onset who were treated with tPA were studied prospectively. Patients with internal carotid artery, M1, and M2 occlusion were enrolled, and independent clinical and MRI factors associated with no early recanalization within 1 hour after tPA administration were examined using multivariate logistic regression analysis. RESULTS: One hundred thirty-two patients (63 men; mean age, 76.4±10.2 years; internal carotid artery occlusion in 37 patients, M1 occlusion in 58, and M2 occlusion in 37) were enrolled. Follow-up MR angiography within 60 minutes after tPA infusion revealed early recanalization in 49 (37.1%) patients (complete in 16 patients, partial in 33) and no recanalization in 83 (62.9%). Using 8 variables (atrial fibrillation, time from stroke onset to treatment ≥140 minutes, use of warfarin, glucose ≥135 mg/dL, large artery diseases, internal carotid artery occlusion, M1 occlusion, and M1 susceptibility vessel sign on T2*) identified on univariate analysis at P<0.2, multivariate logistic regression analysis revealed that M1 susceptibility vessel sign was the only independent factor associated with no early recanalization (OR, 7.157; 95% CI, 1.756 to 29.172; P=0.006). The sensitivity, specificity, positive predictive value, and negative predictive value of M1 susceptibility vessel sign for predicting no early recanalization were 31.3%, 93.9%, 89.7%, and 44.7%, respectively. CONCLUSIONS: Of clinical and MRI factors before tPA infusion, M1 susceptibility vessel sign on T* is the only independent factor associated with no early recanalization within 1 hour after tPA administration.

Utility of the Kurashiki Prehospital Stroke Scale for hyperacute stroke.

BACKGROUNDS: Our aim was to confirm the utility of paramedics using the Kurashiki Prehospital Stroke Scale (KPSS), with a maximum score of 13, for patients who may be eligible for administration of intravenous tissue plasminogen activator (IV t-PA). METHODS: The subjects comprised acute stroke and transient ischemic attack (TIA) patients transferred to our hospital by paramedics. We analyzed correlations between KPSS and the National Institutes of Health Stroke Scale (NIHSS). Patients admitted within 3 h of onset were categorized into 2 groups: KPSS ≥4 and KPSS <4. We compared the proportion of patients receiving IV t-PA between the groups. RESULTS: Among 430 consecutive patients (mean age = 73 years; 266 men), paramedics recorded KPSS for 256 patients (59.5%). Excellent correlation was observed between KPSS and NIHSS in all 256 patients (R = 0.766; p < 0.001) and in 94 patients (ischemic stroke and TIA with symptoms on admission) admitted within 3 h of onset (R = 0.706; p < 0.001). Among these 94 patients, IV t-PA was more frequently given in the KPSS ≥4 group (30 of 58 patients, 51.7%) than in the KPSS <4 group (5 of 36 patients, 13.9%; p < 0.001). Arterial occlusion was more frequently observed in the KPSS ≥4 group (57.9 vs. 31.4%, p = 0.018). KPSS ≥4 was independently associated with administration of IV t-PA (odds ratio = 4.7; 95% confidence interval = 1.5-14.6, p = 0.008). CONCLUSION: Reliable concordance between KPSS and NIHSS was found in acute stroke and TIA patients. KPSS ≥4 represents a good score to indicate prospective t-PA patients among those admitted within 3 h of stroke onset.

Hemorrhagic transformation in acute cerebellar infarction.

BACKGROUND: Hemorrhagic transformation (HT) is a well-known consequence of acute ischemic stroke, but little is known about HT in cerebellar infarction. METHODS: Patients with acute cerebellar infarction within 48 h of onset were retrospectively recruited. MRI, including diffusion-weighted imaging (DWI) and T(2)*-gradient echo imaging (T(2)*), was performed twice (upon admission and 2 weeks after stroke onset). Infarct diameter and volume were measured by manual tracing on initial DWI. HT was evaluated with follow-up T(2)*, and all patients were divided into two groups according to the presence of HT (HT group and non-HT group). The frequency of HT and the factors associated with HT were investigated. RESULTS: Ninety-six patients (64 males, median age 74 years, IQR 65-81 years, and National Institute of Health Stroke Scale score 5, IQR 1-14) were enrolled. Forty-two patients (43%) showed HT on follow-up T(2)* (HT group). Infarct diameter and volume were larger in the HT group than in the non-HT group (3.2 vs. 1.6 cm, respectively, p < 0.001, for infarct diameter and 8.0 vs. 1.7 cm(3), respectively, p < 0.001 for infarct volume). Multivariate logistic regression analysis revealed that both infarct diameter >2.7 cm (OR 7.58, 95% CI 2.82-20.4, p < 0.001) and volume >4.5 cm(3) (OR 11.5, 95% CI 3.80-34.8, p < 0.001) were independent factors associated with HT. CONCLUSIONS: Half of the patients with acute cerebellar infarcts had HT on follow-up T(2)*. Initial infarct diameter and volume on DWI were independent factors associated with HT.