Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes with Alteplase at 0.6 mg/kg in Clinical Practice: THAWS2 Study.

INTRODUCTION: The aim of this study was to determine the safety and efficacy of intravenous (IV) alteplase at 0.6 mg/kg for patients with acute wake-up or unclear-onset strokes in clinical practice. METHODS: This multicenter observational study enrolled acute ischemic stroke patients with last-known-well time >4.5 h who had mismatch between DWI and FLAIR and were treated with IV alteplase. The safety outcomes were symptomatic intracranial hemorrhage (sICH) after thrombolysis, all-cause deaths, and all adverse events. The efficacy outcomes were favorable outcome defined as an mRS score of 0-1 or recovery to the same mRS score as the premorbid score, complete independence defined as an mRS score of 0-1 at 90 days, and change in NIHSS at 24 h from baseline. RESULTS: Sixty-six patients (35 females; mean age, 74 ± 11 years; premorbid complete independence, 54 [82%]; median NIHSS on admission, 11) were enrolled at 15 hospitals. Two patients (3%) had sICH. Median NIHSS changed from 11 (IQR, 6.75-16.25) at baseline to 5 (3-12.25) at 24 h after alteplase initiation (change, -4.8 ± 8.1). At discharge, 31 patients (47%) had favorable outcome and 29 (44%) had complete independence. None died within 90 days. Twenty-three (35%) also underwent mechanical thrombectomy (no sICH, NIHSS change of -8.5 ± 7.3), of whom 11 (48%) were completely independent at discharge. CONCLUSIONS: In real-world clinical practice, IV alteplase for unclear-onset stroke patients with DWI-FLAIR mismatch provided safe and efficacious outcomes comparable to those in previous trials. Additional mechanical thrombectomy was performed safely in them.

Effects of a Disease Management Program for Preventing Recurrent Ischemic Stroke.

Background and Purpose- Disease management is a healthcare strategy that includes self-management education and treatment coordination. We conducted a randomized controlled trial to determine whether a disease management program intervention could improve risk factor profiles and, thus, reduce the recurrence of stroke and other cardiovascular diseases. Methods- This study is a prospective randomized, open-label, parallel group study involving outpatients with a history of stroke. Between September 2010 and November 2012, we enrolled patients aged between 40 and 80 years who experienced their last ischemic stroke event or transient ischemic attack within 1 year. After stratifying by the ischemic stroke subtype, 321 subjects (67.5±8.5 years, 95 female) were randomly assigned to either the disease management program intervention group (n=156) or the usual care group (n=165). The primary end point of this study was the difference in the Framingham risk score (general cardiovascular disease 10-year risk) from baseline. The secondary end points of this study included stroke recurrence, onset of cardiovascular disease, all-cause mortality, and all vascular events. Results- Regarding the primary end point, there was no significant difference in the changes in the Framingham risk score at any follow-up time between the groups. The incidence of stroke recurrence tended to be lower in the disease management program intervention group, although no significant difference was found (hazard ratio, 0.49; 95% CI, 0.19-1.29). Conclusions- We were unable to demonstrate a clear benefit of disease management program intervention. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02121327.

Association Between Absolute Eosinophil Count and Complex Aortic Arch Plaque in Patients With Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Eosinophil counts are thought to be associated with atherosclerosis and aortic arch plaques. However, whether these associations exist among patients with acute ischemic stroke remains unclear. We aimed to evaluate the association between absolute eosinophil count (AEC) and aortic arch plaques among these patients. METHODS: Consecutive acute ischemic stroke patients undergoing transesophageal echocardiography were retrospectively analyzed. Complex aortic arch plaques (CAPs) were defined as plaques ≥4 mm in thickness, with ulcer, or with mobile component. RESULTS: A total of 430 patients (289 male, mean age 69.8±11.4 years) were enrolled. Patients with CAPs (n=169) showed higher mean AEC than those without (167±174/µL versus 127±127/µL; P=0.007). Multivariate analysis showed that increased AEC was independently associated with the presence of CAPs (odds ratio, 2.09; 95% confidence interval, 1.21-3.65). CONCLUSIONS: Among patients with acute ischemic stroke, increased AEC was independently associated with the presence of CAPs. Our results suggest that AEC may be a useful predictor for the presence of CAPs in these patients.

A Case of Hypertensive Encephalopathy with Enlarged Optic Nerve Sheath Measured by Transorbital Sonography.

This case report describes our experience in using transorbital sonography to evaluate pathological changes in the central nervous system in hypertensive encephalopathy. A 49-year-old man with nausea, headache, and mild confusion was diagnosed with hypertensive encephalopathy by brain magnetic resonance imaging (MRI), which revealed vasogenic edema in the bilateral thalamus and the brain stem. Lumbar puncture showed no severe intracranial hypertension. Transorbital sonography showed an increase in the optic nerve sheath diameter (ONSD). Repeated examination revealed a return of the ONSD to an almost normal range after a reduction in blood pressure and a resolution of symptoms. An improvement in cerebral vasogenic edema was confirmed by brain MRI. ONSD might be related to the severity of cerebral vasogenic edema. Repeated measurement of ONSD by transorbital sonography may be useful to assess the pathological course and the effect of treatment in hypertensive encephalopathy.

Non-convulsive status epilepticus with Takotsubo cardiomyopathy: a case report.

A 61-year-old woman was admitted to our hospital for speech disturbance and mild consciousness impairment. Despite the absence of seizures or loss of consciousness, electroencephalographic abnormalities were observed, and the cerebral blood flow scintigraphy revealed an increase in cerebral blood flow in the left temporal lobe. These findings suggested a diagnosis of non-convulsive status epilepticus. On the third day, a twelve-lead electrocardiogram showed a negative T-wave in I, II, aVf, and V2-6. Moreover, a transthoracic echocardiogram revealed left ventricular apical akinesis. However, the coronary angiography showed no evidence of vascular stenotic lesions. We expect the present case report to contribute to the identification of non-convulsive status epilepticus with Takotsubo cardiomyopathy.

Baseline feature of a randomized trial assessing the effects of disease management programs for the prevention of recurrent ischemic stroke.

BACKGROUND: Comprehensive and long-term patient education programs designed to improve self-management can help patients better manage their medical condition. Using disease management programs (DMPs) that were created for each of the risk factor according to clinical practice guidelines, we evaluate their influence on the prevention of stroke recurrence. METHODS: This is a randomized study conducted with ischemic stroke patients within 1 year from their onset. Subjects in the intervention group received a 6-month DMPs that included self-management education provided by a nurse along with support in collaboration with the primary care physician. Those in the usual care group received ordinary outpatient care. The primary end point is a difference of the Framingham risk score-general cardiovascular disease 10-year risk [corrected]. Patients were enrolled for 2 years with plans for a 2-year follow-up after the 6-month education period (total of 30 months). RESULTS: A total of 321 eligible subjects (average age, 67.3 years; females, 96 [29.9%]), including 21 subjects (6.5%) with transient ischemic attack, were enrolled in this study. Regarding risk factors for stroke, 260 subjects (81.0%) had hypertension, 249 subjects (77.6%) had dyslipidemia, 102 subjects (31.8%) had diabetes mellitus, 47 subjects (14.6%) had atrial fibrillation, and 98 subjects (30.5%) had chronic kidney disease. There were no significant differences between the 2 groups with respect to subject characteristics. CONCLUSIONS: This article describes the rationale, design, and baseline features of a randomized controlled trial that aimed to assess the effects of DMPs for the secondary prevention of stroke. Subject follow-up is in progress and will end in 2015.

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.

[A case of polyarteritis nodosa with giant intracranial aneurysm].

A 46-year-old man with a history of the left retinal central artery obstruction and old cerebral infarction in the right middle cerebral artery region presented with right total blindness due to the right retinal central artery occlusion accompanied by a cherry red spot. He had been found to have a giant, 17 mm-in-diameter aneurysm of the right internal carotid artery and a right vertebral arterial aneurysm. The intra-arterial thrombolysis was performed with urokinase injection for the right eye artery origin, and the right eyesight has improved. Cranial and pelvic angiography showed multiple stenosis and dilatation of external carotid and internal iliac arteries. The right superficial temporal artery biopsy revealed the arteritis with fibrinoid necrosis. He was diagnosed as having polyarteritis nodosa (PAN) by clinical course, angiography, and the superficial temporal artery biopsy. Several studies have reported that PAN had less intracranial aneurysm and the diameter of the aneurysm was less than 5 mm. Our case is the first report that PAN had giant aneurysm of 17 mm, diagnosed by temporal artery biopsy. The temporal artery biopsy should be considered to diagnose PAN.

Early ischaemic diffusion lesion reduction in patients treated with intravenous tissue plasminogen activator: infrequent, but significantly associated with recanalization.

BACKGROUND AND PURPOSE: Recent studies have shown that thrombolysis could decrease or eliminate ischaemic diffusion-weighted imaging lesions. However, the features of such diffusion-weighted imaging lesion reduction are not well known. AIMS: To clarify, the frequency of and factors associated with lesion reduction were investigated. METHODS: Patients given intravenous tissue plasminogen activator therapy within three-hours of onset were prospectively enrolled. Magnetic resonance imaging including diffusion-weighted imaging and magnetic resonance angiography was performed four times: on admission, just after intravenous tissue plasminogen activator, 24 h from intravenous tissue plasminogen activator, and seven-days after intravenous tissue plasminogen activator. The diffusion-weighted imaging lesion volume was measured by manual trace using National Institutes of Health imaging software. All patients were divided into three groups according to the early diffusion-weighted imaging lesion volume change from admission to just after intravenous tissue plasminogen activator: the lesion reduction group (>20% decrease); the lesion growth group (>20% increase); and the lesion unchanged group. RESULTS: In total, 105 patients [56 males, median age 77 (interquartile range 70-83) years, and National Institutes of Health Stroke Scale score 16 (10-22)] were enrolled. Early diffusion-weighted imaging lesion reduction was observed in seven (7%) patients. The decreased lesion increased subsequently. On multivariate analysis, the glucose level on admission (odds ratio 0·95, 95% confidence interval 0·91 to 0·99, P = 0·045) and early recanalization (odds ratio 15·7, 95% confidence interval 1·61 to 153, P = 0·018) were independently related to early lesion reduction. CONCLUSION: Early diffusion-weighted imaging lesion reduction was observed in 7% of patients treated with intravenous tissue plasminogen activator. The decreased lesion increased subsequently. Initial glucose level and early recanalization were independently associated with early diffusion-weighted imaging lesion reduction.

Acute stroke patients have occult malignancy more often than expected.

The aim of the present study was to investigate the frequency of having occult malignancy in patients with acute ischemic stroke and their clinical characteristics. We retrospectively enrolled 1,714 consecutive ischemic stroke patients within 7 days of onset. The patients were divided into two groups: the Non-M group had no malignancy, and the M group had malignancy. We compared the clinical characteristics of the two groups. Of 1,714 ischemic stroke patients, 51 patients (3.0%; M group) were newly diagnosed as having malignancy. The M group was significantly older than the Non-M group (p = 0.009). Hemoglobin (Hb) was less and D-dimer was higher in the M group than in the Non-M group (p < 0.001). The patients with both D-dimer >or=1.3 ng/dl and Hb <12.8 g/dl more frequently had occult malignancy than patients without (p = 0.0088).

Plasma brain natriuretic peptide as an independent predictor of in-hospital mortality after acute ischemic stroke.

BACKGROUND AND PURPOSE: We investigated whether the plasma brain natriuretic peptide (BNP) level on admission can serve as a biological marker of in-hospital death in patients with acute ischemic stroke. METHODS: We prospectively enrolled 335 consecutive patients (125 females; mean age, 72.3 years) with acute ischemic stroke within 24 hours of onset and measured plasma BNP on admission. Patients were divided into two groups: the deceased group, who died during hospitalization; and the survival group. The factors associated with in-hospital death were investigated by multivariate logistic regression analysis. RESULTS: Death was observed in 20 (6.0%) patients. Frequencies of atrial fibrillation, cardioembolism, the use of diuretics before ischemic stroke, the use of digitalis before ischemic stroke, National Institutes of Health Stroke Scale (NIHSS) score on admission, glucose level, and D-dimer were significantly higher in the deceased group than in the survival group. On the other hand, albumin was significantly lower in the deceased group than in the survival group. The mean +/- SD of the plasma BNP level of the deceased group was significantly higher than that of the survival group (731.5+/-1,070.9 vs. 213.1+/-384.5 pg/mL, p=0.001). The optimal cut-off level, sensitivity, and specificity of BNP levels to distinguish the deceased group from the survival group were 240 pg/mL, 75.0% and 73.0%, respectively. Multivariate logistic regression analysis demonstrated that a NIHSS score of >13 (odds ratio [OR], 4.87; 95% confidence interval, 1.54 to 15.44, p=0.007) and plasma BNP level of >240 pg/mL (OR, 4.67; 95% confidence interval, 1.28 to 17.09, p=0.020) were independent factors associated with in-hospital death. CONCLUSION: The plasma BNP level on admission can predict in-hospital death in patients with acute ischemic stroke.

[A case of pontine infarction presenting with conjugate deviation and unilateral conjugate gaze palsy].

We reported a case of pontine infarction presenting with conjugate deviation and unilateral conjugate gaze palsy. A 75-year-old man was admitted to our hospital because of vomiting. On the day of admission, his neurological findings showed only conjugate deviation to the right without consciousness disturbance, hemispatial neglect, and hemiparesis. On day 5 after admission, the conjugate deviation to the right disappeared, but he could not gaze left with either of his eyes. The pathological lesions, therefore, were considered to be a unilateral paramedian pontine reticular formation (PPRF) and abducens nucleus. Diffusion-weighted imaging (DWI) on day 2 revealed a small high intensity lesion in the left paramedian pontine tegmentum. A diagnosis of brain infarction was made. A Holter electrocardiogram and electroencephalogram were normal. Transesophageal echocardiography disclosed ulcerated plaque in the aortic arch. This is the first case of pontine infarction presenting with conjugate deviation in which unilateral conjugate gaze palsy and DWI could confirm the pathological lesion.

[A cardioembolic stroke case involving both the posterior cerebral artery and anterior choroidal artery territories].

We reported a rare case of cardioembolic stroke involving the territories of both the posterior cerebral artery (PCA) and the anterior choroidal artery. An 86-year-old man with atrial fibrillation was admitted to our hospital with consciousness disturbance and left hemiparesis. Diffusion-weighted imaging revealed high intensity lesions in the territories of the PCA and the anterior choroidal artery, leading us to make a diagnosis of cardioembolic stroke. Magnetic resonance angiography disclosed occlusion of the right internal carotid artery (ICA) and the right PCA. The P1 segment of the right PCA was absent, indicating that the right PCA had branched from the right ICA. Therefore, we believed that ICA occlusion caused the infarcts in the territories of both the PCA and the anterior choroidal artery. This is a rare stroke case involving the territories of both the PCA and the anterior choroidal artery.