Takuya Okata

Dissolution of the Left Atrial Appendage Thrombus with Rivaroxaban Therapy

apy [2, 3] . Recently, novel oral anticoagulants (NOACs) have emerged as alternative prophylaxis for thromboembolism in patients with nonvalvular AF. However, the effect of NOACs on intracardiac thrombi has not been fully elucidated. Here we report on the dissolution of LAA thrombus in 3 patients with nonvalvular AFrelated stroke receiving rivaroxaban. The clinical and neuroradiological characteristics of the 3 patients are summarized in table 1 .

Blood Pressure Variability on Antihypertensive Therapy in Acute Intracerebral Hemorrhage The Stroke Acute Management With Urgent Risk-Factor Assessment and Improvement-Intracerebral Hemorrhage Study

Background and Purpose— The associations between early blood pressure (BP) variability and clinical outcomes in patients with intracerebral hemorrhage after antihypertensive therapy, recently clarified by a post hoc analysis of Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT2), were confirmed using the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-intracerebral hemorrhage study cohort. Methods— Patients with hyperacute (<3 hours from onset) intracerebral hemorrhage with initial systolic BP (SBP) >180 mm Hg were registered in a prospective, multicenter, observational study. All patients received antihypertensive therapy based on a predefined standardized protocol to lower and maintain SBP between 120 and 160 mm Hg using intravenous nicardipine. BPs were measured hourly during the initial 24 hours. BP variability was determined as SD and successive variation. The associations between BP variability and hematoma expansion (>33%), neurological deterioration within 72 hours, and unfavorable outcome (modified Rankin Scale, 4–6) at 3 months were assessed. Results— Of the 205 patients, 33 (16%) showed hematoma expansion, 14 (7%) showed neurological deterioration, and 81 (39%) had unfavorable outcomes. The SD and successive variation of SBP were 13.8 (interquartile range, 11.5–16.8) and 14.9 (11.7–17.7) mm Hg, respectively, and those of diastolic BP were 9.4 (7.5–11.2) and 13.1 (11.2–15.9) mm Hg, respectively. On multivariate regression analyses, neurological deterioration was associated with the SD of SBP (odds ratio, 2.75; 95% confidence interval, 1.45–6.12 per quartile) and the successive variation of SBP (2.37; 1.32–4.83), and unfavorable outcome was associated with successive variation of SBP (1.42; 1.04–1.97). Hematoma expansion was not associated with any BP variability. Conclusions— SBP variability during the initial 24 hours of acute intracerebral hemorrhage was independently associated with neurological deterioration and unfavorable outcomes. Stability of antihypertensive therapy may improve clinical outcomes.

Spontaneous heparin-induced thrombocytopenia syndrome without any proximate heparin exposure, infection, or inflammatory condition: Atypical clinical features with heparin-dependent platelet activating antibodies

Abstract Recent studies suggest that a thromboembolic disorder resembling heparin-induced thrombocytopenia (HIT), so-called spontaneous HIT syndrome, can occur in patients without any history of heparin exposure. It is likely due to anti-platelet factor 4 (PF4)/polyanion antibodies induced by other polyanions, such as bacterial surfaces and nucleic acids. We describe an atypical case of spontaneous HIT syndrome. A 70-year-old man suddenly presented with acute cerebral sinus thrombosis (CST). Soon after the initiation of unfractionated heparin (UFH) for the treatment of CST, his platelet count fell precipitously and he developed deep vein thrombosis, a clinical picture consistent with rapid-onset HIT but without any proximate episodes of heparin exposure, infection, trauma, surgery, or other acute illness. Antigen assays and a washed platelet activation assay indicated that the patient already possessed anti-PF4/heparin IgG antibodies with heparin-dependent platelet activation properties on admission. Cessation of UFH and initiation of argatroban resulted in prompt recovery of his platelet count without further thromboembolic events. We identified two similar cases in the literature. However, these patients do not meet the recently proposed criteria for spontaneous HIT syndrome. Even in atypical cases, however, inappropriate or delayed diagnosis of HIT appears to be associated with worse outcomes. We propose that these atypical cases should be included in the category of spontaneous HIT syndrome.

Anticoagulation Intensity of Rivaroxaban for Stroke Patients at a Special Low Dosage in Japan

Objectives In Japan, low-dose rivaroxaban [15 mg QD/10 mg QD for creatinine clearance of 30–49 mL/min] was approved for clinical use in NVAF patients partly because of its unique pharmacokinetics in Japanese subjects. The aim of the study was to determine the anticoagulation intensity of rivaroxaban and its determinant factors in Japanese stroke patients. Methods Consecutive stroke patients with NVAF admitted between July 2012 and December 2013 were studied. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and estimated plasma concentration of rivaroxaban (Criv) based on an anti-factor Xa chromogenic assay were measured just before and 4 and 9 h after administration at the steady state level of rivaroxaban. Determinant factors for Criv were explored using a linear mixed-model approach. Results Of 110 patients (37 women, 75±9 years old), 59 took 15 mg QD of rivaroxaban and 51 took 10 mg QD. Criv at 4 h was 186 ng/mL for patients taking 15 mg QD and 147 ng/mL for those taking 10 mg QD. Both PT and aPTT were positively correlated with Criv. Criv was 72% lower at 4 h in 15 patients receiving crushed tablets than in the other patients, and tablet crushing was significantly associated with lower Criv (adjusted estimate −0.43, 95% CI −0.60 to −0.26) after multivariate-adjustment. Conclusion The anticoagulation effects of rivaroxaban in the acute stroke setting for Japanese NVAF patients were relatively low as compared with those in the ROCKET-AF and J-ROCKET AF trials. Tablet crushing, common in dysphagic patients, decreased Criv.

Relative systolic blood pressure reduction and clinical outcomes in hyperacute intracerebral hemorrhage: the SAMURAI-ICH observational study.

Background and purpose: Blood pressure lowering is often performed as a part of general acute management in acute intracerebral hemorrhage (ICH) patients. The relationship between relative blood pressure reduction and clinical outcomes is not fully known. Methods: Hyperacute (<3 h from onset) ICH patients with initial SBP more than 180 mmHg were included in the observational study. All patients received intravenous antihypertensive treatment based on a predefined protocol to lower and maintain SBP between 120 and 160 mmHg. The relative SBP reduction was defined as the ratio of SBP reduction to the admission SBP in the first 24 h, and associations between the relative SBP reduction and neurological deterioration (≥2 points decrease in the Glasgow Coma Scale score or ≥4 increase in the National Institutes of Health Stroke Scale score), hematoma expansion (>33% increase), and unfavorable outcome (modified Rankin scale score 4–6 at 3 months) were assessed with multivariate logistic regression analyses. Results: Of the 211 patients [81 women, median age 65 (interquartile range 58–74) years, and median initial National Institutes of Health Stroke Scale score 13 (8–17)] enrolled, 17 (8%) showed neurological deterioration, 36 (17%) showed hematoma expansion, and 87 (41%) had an unfavorable outcome. On multivariate regression analyses, relative SBP reduction was independently and inversely associated with neurological deterioration (odds ratio 0.053, 95% confidence interval 0.011–0.254 per 10% increment), hematoma expansion (0.289, 0.099–0.841), and unfavorable outcome (0.254, 0.095–0.680) after adjusting for known predictive factors. Conclusion: Insufficient relative SBP reduction after standardized antihypertensive therapy in hyperacute ICH was independently associated with poor clinical outcomes. Aggressive antihypertensive treatment may improve clinical outcomes.

Continuous Antihypertensive Therapy Throughout the Initial 24 Hours of Intracerebral Hemorrhage: The Stroke Acute Management With Urgent Risk-Factor Assessment and Improvement–Intracerebral Hemorrhage Study

Background and Purpose— A short duration (<24 hours) of antihypertensive therapy (AHT) after acute intracerebral hemorrhage (ICH) may be sufficient because active bleeding generally ceases within several hours. We aimed to determine the association between sequential systolic blood pressure (SBP) levels during AHT and outcomes in ICH patients. Methods— In 211 hyperacute ICH patients who underwent AHT based on predefined protocol, the mean of hourly SBP (mSBP) measurements was calculated over 1 to 8 hours (first mSBP), 9 to 16 hours (second mSBP), and 17 to 24 hours (third mSBP) after the initiation of AHT. Outcomes included neurological deterioration (72-hour Glasgow Coma Scale decrease ≥2 or National Instititutes of Health Stroke Scale increase ≥4), hematoma expansion (>33%), and unfavorable outcome (3-month modified Rankin Scale score 4–6). Results— The median first, second, and third mSBPs were 132, 131, and 137 mm Hg, respectively. A higher first mSBP (odds ratio [OR], 2.41; 95% confidence interval [CI], 1.34–4.69 per 10 mm Hg) or second mSBP (OR, 2.08; 95% CI, 1.20–3.80) was independently associated with neurological deterioration, and a higher second mSBP (OR, 1.40; 95% CI, 1.02–2.00) or third mSBP (OR, 1.45; 95% CI, 1.05–2.05) was associated with unfavorable outcome. None of the mSBPs was associated with hematoma expansion. Conclusions— The continuation of AHT throughout the initial 24 hours after ICH may improve outcomes.

Subacute Methotrexate Encephalopathy Mimicking Ischemic Stroke With Dynamic Changes on Magnetic Resonance Imaging

We report a 35-year-old woman who suddenly developed left hemiparesis and dysarthria at 13days after treatment with intrathecal and intravenous methotrexate for intravascular large B cell lymphoma with possible central nervous system infiltration. Seven hours after onset, she developed further right hemiparesis and aphasia. However, the majority of neurologic symptoms disappeared spontaneously and completely by 34hours. We also recorded the dynamic progression and regression of abnormal signals in the bilateral corona radiata on diffusion-weighted imaging, in parallel with neurologic symptoms. The rapid reversal of MR abnormalities and neurologic symptoms allowed us to diagnose methotrexate encephalopathy, and exclude intravascular large B cell lymphoma recurrence and regular brain infarction. The case provides new data on the dynamic changes of abnormal signals on magnetic resonance imaging in methotrexate encephalopathy over a short recovery time.

Associations between Pre-Admission Risk Scores and Two-Year Clinical Outcomes in Ischemic Stroke or Transient Ischemic Attack Patients with Non-Valvular Atrial Fibrillation

Background: We aimed to clarify associations between pre-admission risk scores (CHADS2, CHA2DS2-VASc, and HAS-BLED) and 2-year clinical outcomes in ischemic stroke or transient ischemic attack (TIA) patients with non-valvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry. Methods: From 18 Japanese stroke centers, ischemic stroke or TIA patients with NVAF hospitalized within 7 days after onset were enrolled. Outcome measures were defined as death/disability (modified Rankin Scale score ≥3) at 2 years, 2-year mortality, and ischemic or hemorrhagic events within 2 years. Results: A total of 1,192 patients with NVAF (527 women; mean age, 78 ± 10 years), including 1,141 ischemic stroke and 51 TIA, were analyzed. Rates of death/disability, mortality, and ischemic or hemorrhagic events increased significantly with increasing pre-admission CHADS2 (p for trend <0.001 for death/disability and mortality, p for trend = 0.024 for events), CHA2DS2-VASc (p for trend <0.001 for all), and HAS-BLED (p for trend = 0.004 for death/disability, p for trend <0.001 for mortality, p for trend = 0.024 for events) scores. Pre-admission CHADS2 (OR per 1 point, 1.52; 95% CI 1.35–1.71; p <0.001 for death/disability; hazard ratio (HR) per 1 point, 1.23; 95% CI 1.12–1.35; p <0.001 for mortality; HR per 1 point, 1.14; 95% CI 1.02–1.26; p = 0.016 for events), CHA2DS2-VASc (1.55, 1.41–1.72, p < 0.001; 1.21, 1.12–1.30, p < 0.001; 1.17, 1.07–1.27, p < 0.001; respectively), and HAS-BLED (1.33, 1.17–1.52, p < 0.001; 1.23, 1.10–1.38, p < 0.001; 1.18, 1.05–1.34, p = 0.008; respectively) scores were independently associated with all outcome measures. Conclusions: In ischemic stroke or TIA patients with NVAF, all pre-admission risk scores were independently associated with death/disability at 2 years and 2-year mortality, as well as ischemic or hemorrhagic events within 2 years.

Low DWI-ASPECTS is associated with atrial fibrillation in acute stroke with the middle cerebral artery trunk occlusion.

BACKGROUND AND PURPOSE For optimal acute stroke management and secondary prevention, discrimination of stroke etiology is crucial. We hypothesized that a low Alberta Stroke Program Early CT Score (ASPECTS) on diffusion-weighted imaging (DWI) immediately after stroke onset was associated with the presence of atrial fibrillation (AF). METHODS Consecutive patients admitted within 24h from stroke onset with an occlusion at the horizontal segment of the middle cerebral artery (M1) on initial MRA were retrospectively enrolled. AF was diagnosed based on continuous electrocardiogram monitoring during acute hospitalization or its confirmed history. RESULTS Of the 206 patients (95 women, median age 77 [IQR 69-85] years, NIHSS score 18 [13-23]) enrolled, AF was identified in 138 patients (AF group): chronic AF in 89, known paroxysmal AF (pAF) in 13, and masked pAF on admission in 36. The ASPECTS score on the initial DWI, performed a median of 2.5h after onset, was lower in the AF group than in the others (4 [2-6] vs. 7 [4-8], p<0.001). With the optimal cut-off value of ≤ 6 (sensitivity, 78%; specificity, 57%; area under the ROC curve, 0.682), DWI-ASPECTS was independently associated with the presence of any AF (OR 5.05, 95%CI 2.36 to 10.8), as well as the presence of any pAF (OR 8.64, 95%CI 3.00 to 24.9) and that of masked pAF on admission (OR 10.0, 95%CI 3.06 to 32.9). CONCLUSION Extensive early ischemic change assessed by DWI-ASPECTS predicts the presence of AF, even initially masked pAF, in acute stroke patients with M1 occlusion.