Masaki Naganuma

Routine Use of Intravenous Low-Dose Recombinant Tissue Plasminogen Activator in Japanese Patients General Outcomes and Prognostic Factors From the SAMURAI Register

Background and Purpose— A retrospective, multicenter, observational study was conducted to document clinical outcomes and to identify outcome predictors in patients treated with low-dose intravenous recombinant tissue plasminogen activator (0.6 mg/kg alteplase), which was approved in Japan in 2005, within 3 hours of stroke onset. Methods— Consecutive patients with stroke treated with recombinant tissue plasminogen activator in 10 Japanese stroke centers were included. Results— A total of 600 patients (377 men, 72±12 years old) were studied. Median National Institutes of Health Stroke Scale scores decreased from 13 before recombinant tissue plasminogen activator to 8 at 24 hours later. Symptomatic intracerebral hemorrhage within 36 hours with a ≥1-point increase from the baseline National Institutes of Health Stroke Scale score developed in 23 patients (3.8%; 95% CI, 2.6% to 5.7%). At 3 months, 43 patients had died (7.2%; 5.4% to 9.5%), and 199 patients (33.2%; 29.5% to 37.0%) had a modified Rankin Scale score ≤1. Analysis of 399 patients with a premorbid modified Rankin Scale score ≤1 who met the criteria of the European license (≤80 years old, an initial National Institutes of Health Stroke Scale score ≤24, etc) showed that 40.6% (35.9% to 45.5%) had a 3-month modified Rankin Scale score ≤1. After multivariate adjustment, younger age, lower initial National Institutes of Health Stroke Scale score, absence of internal carotid artery occlusion, higher Alberta Stroke Program Early CT Score on CT, and absence of intravenous antihypertensives just before recombinant tissue plasminogen activator were independently related to a 3-month modified Rankin Scale score ≤1. Congestive heart failure and hyperglycemia were independently related to mortality. Conclusions— Three-month outcomes of patients receiving low-dose intravenous recombinant tissue plasminogen activator therapy in the present study were similar to those from postmarketing surveys using 0.9 mg/kg alteplase.

Reduced Estimated Glomerular Filtration Rate Is Associated with Stroke Outcome after Intravenous rt-PA: The Stroke Acute Management with Urgent Risk-Factor Assessment and Improvement (SAMURAI) rt-PA Registry

Background: The aim of this study was to determine whether renal dysfunction affects the outcome of stroke patients treated with recombinant tissue plasminogen activator (rt-PA). Methods: A retrospective, multicenter, observational study was conducted to identify the effects of underlying risk factors on intravenous rt-PA therapy using 0.6 mg/kg alteplase in 10 stroke centers in Japan. Consecutive stroke patients with a premorbid modified Rankin Scale (mRS) score ≤3 who received rt-PA were studied. Renal dysfunction was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 on admission. The outcome measures were any intracerebral hemorrhage (ICH) and symptomatic ICH within the initial 36 h; favorable (mRS 0–1) outcome, poor outcome (mRS 4–6) and mortality at 3 months. Results: Of a total of 578 patients (372 men; 64.4%, 71.4 ± 11.7 years old), renal dysfunction was present in 186 patients (32.2%). These patients were older and more commonly had hypertension, atrial fibrillation, prior ischemic heart disease and prior use of antithrombotic agents than patients without renal dysfunction. ICH (27.4 vs. 16.6%) and symptomatic ICH (8.1 vs. 2.6%) was more common in patients with renal dysfunction than in those without. At 3 months, patients with renal dysfunction had higher median mRS scores than those without (3 vs. 2). After multivariate adjustment for established outcome predictors, renal dysfunction was related to any ICH (odds ratio 1.81, 95% confidence interval 1.16–2.84), symptomatic ICH (2.64, 1.10–6.56), poor outcome (1.55, 1.01–2.38), and mortality (2.94, 1.38–6.42). Conclusions: Reduced eGFR was associated with early ICH and 3-month unfavorable outcome in stroke patients receiving intravenous rt-PA.

Pretreatment ASPECTS on DWI predicts 3-month outcome following rt-PA: SAMURAI rt-PA Registry

Objective: To evaluate whether the pretreatment Alberta Stroke Programme Early CT Score (ASPECTS) assessed using diffusion-weighted imaging (DWI) predicts stroke outcomes at 3 months following IV recombinant tissue-type plasminogen activator (rt-PA) therapy. Methods: Stroke patients treated with rt-PA (0.6 mg/kg alteplase) in 10 stroke centers in Japan were retrospectively studied. ASPECTS was assessed on DWI just prior to rt-PA injection. The primary outcome was a modified Rankin Scale (mRS) score of 0–2 at 3 months. Secondary outcomes included death at 3 months and symptomatic intracerebral hemorrhage (sICH) within 36 hours. Results: For the 477 patients (316 men, 71 ± 11 years old) enrolled, the median NIH Stroke Scale score was 13 (interquartile range 7–18.5), the median ASPECTS on DWI was 8 (7–10), and sICH was identified in 15 patients (3.1%). At 3 months, 245 (51.4%) had an mRS score of 0–2, and 29 (6.1%) had died. Patients with an mRS score of 0–2 had higher median ASPECTS (9; interquartile range 8–10) than other patients (8; 6–9, p < 0.001). Using receiver operating characteristic curves, the optimal cutoff ASPECTS to predict an mRS score of 0–2 was ≥7. On multivariate regression analysis, ASPECTS ≥7 was related to an mRS score of 0–2 (odds ratio 1.85; 95% confidence interval 1.07–3.24), ASPECTS ≤4 was related to death (3.61; 1.23–9.91), and ASPECTS ≤5 was related to sICH (4.74; 1.54–13.64). Conclusion: ASPECTS on DWI was independently predictive of functional and vital outcomes at 3 months, as well as sICH within 36 hours, following rt-PA therapy for stroke patients.

Early Ischemic Change on CT Versus Diffusion-Weighted Imaging for Patients With Stroke Receiving Intravenous Recombinant Tissue-Type Plasminogen Activator Therapy: Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) rt-PA Registry

Background and Purpose— Alberta Stroke Programme Early CT Score (ASPECTS) is a quantitative topographical score to evaluate early ischemic change in the middle cerebral arterial territory on CT as well as on diffusion-weighted imaging (DWI). The aim of the present study was to elucidate the relationship between CT-ASPECTS and DWI-ASPECTS for patients with hyperacute stroke and their associations with outcomes after recombinant tissue-type plasminogen activator therapy based on a multicenter registry. Methods— ASPECTS was assessed on both CT and DWI before intravenous 0.6 mg/kg alteplase in 360 patients with stroke (119 women, 71±11 years old). The outcomes were symptomatic intracerebral hemorrhage within 36 hours and independence at 3 months defined by a modified Rankin Scale score of 0 to 2. Results— DWI-ASPECTS was positively correlated with CT-ASPECTS (&rgr;=0.511, P<0.001) and was lower than CT-ASPECTS (median 8 [interquartile range, 6 to 9] versus 9 [8 to 10], P<0.001). Higher baseline National Institutes of Health Stroke Scale score (standardized partial regression coefficient [&bgr;] 0.061, P<0.001) and cardioembolic stroke (&bgr; 0.35, P<0.001) were related to this discrepancy. The area under the receiver operating characteristic curve for predicting sICH (12 patients) using ASPECTS was 0.673 (95% CI, 0.503 to 0.807) by CT and 0.764 (95% CI, 0.635 to 0.858) by DWI (P=0.275). The area for predicting independence at 3 months (192 patients) was 0.621 (0.564 to 0.674) by CT and 0.639 (0.580 to 0.694) by DWI (P=0.535). Conclusions— For patients with hyperacute stroke, DWI-ASPECTS scored approximately 1 point lower than CT-ASPECTS. Both CT-ASPECTS and DWI-ASPECTS were useful predictors of symptomatic intracerebral hemorrhage and independence at 3 months after recombinant tissue-type plasminogen activator.

Effects of 24-Hour Blood Pressure and Heart Rate Recorded With Ambulatory Blood Pressure Monitoring on Recovery From Acute Ischemic Stroke

Background and Purpose— This study used ambulatory blood pressure (BP) monitoring to generate BP and heart rate (HR) profiles soon after stroke onset and evaluated the association between determined values and 3-month stroke outcomes. Methods— We analyzed 24-hour ambulatory BP monitoring records from 104 patients with acute ischemic stroke. Ambulatory BP monitoring was attached at the second and eighth hospitalization days (Days 1 and 7). Both BP and HR were characterized using baseline, mean, maximum, and minimum values and coefficient of variation during 24-hour recording periods. Outcomes at 3 months were assessed as independence according to a modified Rankin Scale score of ⩽2 and poor according to the score of ≥5. Results— Sixty-six (63%) patients achieved independence and 12 (11%) had poor outcomes. Mean ambulatory BP monitoring values changed from 150.5±19.5/85.7±11.3 mm Hg on Day 1 to 139.6±19.3/80.0±11.7 mm Hg on Day 7. After multivariate adjustment, mean values of systolic BP (OR, 0.63; 95% CI, 0.45–0.85), diastolic BP (0.61; 0.37–0.98), pulse pressure (0.55; 0.33–0.85), and HR (0.61; 0.37–0.98) recorded on Day 1 as well as mean HR on Day 7 (0.47; 0.23–0.87) were inversely associated with independence and mean values of systolic BP (1.92; 1.15–3.68), diastolic BP (5.28; 1.92–22.85), and HR (4.07; 1.83–11.88) on Day 1 as well as mean HR on Day 7 (4.92; 1.36–36.99) were positively associated with a poor outcome. Conclusions— All of systolic BP, diastolic BP, pulse pressure, and HR on Day 1 and HR on Day 7 assessed using ambulatory BP monitoring were associated with outcomes of patients with stroke at 3 months.

Hyperammonemic encephalopathy caused by urinary tract infection with urinary retention

An 80-year-old female became somnolent and was emergently admitted to our hospital. The patient had a history of urinary retention and recurrent urinary tract infection. She had no history of liver disease. On admission, her blood pressure was 150/90 mm Hg, and her pulse was 110/min and irregular. Her Glasgow Coma Scale score was 8. There were no focal neurological deficits. The plasma ammonia level was elevated to 151 μg/dl (normal, b50 μg/dl). Blood tests showed a leukocytosis (10.7×10 /l), as well as increased serum C-reactive protein (1.78 mg/dl), urea nitrogen (33 mg/dl), and creatinine (1.45 mg/dl) levels. The serum electrolytes and liver function tests were normal. Arterial blood gas analysis showed a mild alkalosis. Cerebrospinal fluid analysis was normal. On computed tomography (CT) and

Early neurological deterioration within 24 hours after intravenous rt-PA therapy for stroke patients: the Stroke Acute Management with Urgent Risk Factor Assessment and Improvement rt-PA Registry.

Background: The initial 24 h after thrombolysis are critical for patients’ conditions, and continuous neurological assessment and blood pressure measurement are required during this time. The goal of this study was to identify the clinical factors associated with early neurological deterioration (END) within 24 h of stroke patients receiving intravenous recombinant tissue plasminogen activator (rt-PA) therapy and to clarify the effect of END on 3-month outcomes. Methods: A retrospective, multicenter, observational study was conducted in 10 stroke centers in Japan. A total of 566 consecutive stroke patients [211 women, 72 ± 12 years old, the median initial NIH Stroke Scale (NIHSS) score of 13] treated with intravenous rt-PA (0.6 mg/kg alteplase) was studied. END was defined as a 4-point or greater increase in the NIHSS score at 24 h from the NIHSS score just before thrombolysis. Results: END was present in 56 patients (9.9%, 18 women, 72 ± 10 years old) and was independently associated with higher blood glucose [odds ratio (OR) 1.17, 95% confidence intervals (CI) 1.07–1.28 per 1 mmol/l increase, p < 0.001], lower initial NIHSS score (OR 0.92, 95% CI 0.87–0.97 per 1-point increase, p = 0.002), and internal carotid artery (ICA) occlusion (OR 5.36, 95% CI 2.60–11.09, p < 0.001) on multivariate analysis. Symptomatic intracranial hemorrhage within the initial 36 h from thrombolysis was more common in patients with END than in the other patients (per NINDS/Cochrane protocol, OR 10.75, 95% CI 4.33–26.85, p < 0.001, and per SITS-MOST protocol, OR 12.90, 95% CI 2.76–67.41, p = 0.002). At 3 months, no patients with END had a modified Rankin Scale (mRS) score of 0–1. END was independently associated with death and dependency (mRS 3–6, OR 20.44, 95% CI 6.96–76.93, p < 0.001), as well as death (OR 19.43, 95% CI 7.75–51.44, p < 0.001), at 3 months. Conclusions: Hyperglycemia, lower baseline NIHSS score, and ICA occlusion were independently associated with END after rt-PA therapy. END was independently associated with poor 3-month stroke outcome after rt-PA therapy.

Rotational vertigo associated with parietal cortical infarction

A 65-year-old woman experienced sudden positional vertigo with rightward, horizontal nystagmus that resolved within days. MRI revealed a left parietal lobe infarction involving the supramarginal gyrus. The patient experienced a transient recurrence of vertigo after 7 days but MRI failed to reveal the presence of any new lesions; furthermore, the patients EEG was normal. We suggest that this patients vertigo was due to her parietal cortical infarction.

Effect of Serum Lipid Levels on Stroke Outcome after rt-PA Therapy: SAMURAI rt-PA Registry

Background: The effects of lipid levels on clinical outcomes after ischemic stroke are controversial. Whether admission lipid levels and prior statin use are associated with early intracerebral hemorrhage (ICH) and long-term functional outcome after recombinant tissue plasminogen activator (rt-PA) therapy for stroke patients was investigated. Methods: Ischemic stroke patients who received intravenous rt-PA from a multicenter registry were studied. Lipid levels on admission, including total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and triglyceride levels, as well as prior statin use, were assessed. The primary outcome was favorable outcome at 3 months corresponding to a modified Rankin Scale score ≤1. The secondary outcome was any or symptomatic ICH within the initial 36 h. Results: Of 489 enrolled patients (171 women, 70.8 ± 11.6 years old), 60 used statins prior to stroke, 93 developed ICH (19.0%), and 188 (38.4%) had a favorable 3-month outcome. Of the lipid levels, only the HDL-C level was an independent predictor of favorable outcome after multivariate adjustment for baseline characteristics (OR 1.95, 95% CI 1.10–3.47 per 1 mmol/l; p = 0.023) and after further adjustment for pretreatment radiological findings (OR 2.03, 95% CI 1.07–3.84; p = 0.029). For the 187 stroke patients without cardioembolism, the HDL-C level was more strongly associated with favorable outcome (OR 4.94, 95% CI 1.91–12.76 per 1 mmol/l; p = 0.001). There were no significant associations between ICH and any lipid levels. Prior statin use was not associated with outcomes. Conclusions: The admission HDL-C level was associated with favorable outcome 3 months after intravenous rt-PA therapy in stroke patients without cardioembolism.

Ulcerated plaques in the aortic arch contribute to symptomatic multiple brain infarction

Background The configuration of aortic plaque appears to be as important as its thickness when it acts as an embolic source to the brain. The frequency and clinical predictors of ulcerated plaque at the aortic arch identified using transoesophageal echocardiography (TOE) in patients with stroke were determined, and the association between the ulcer and recent ischaemic stroke, particularly multiple brain infarcts, which appear to indicate embolic stroke, was examined. Methods Aortic and cardiac embolic sources were evaluated using TOE in 360 patients with fresh ischaemic stroke proven by diffusion-weighted MRI, including 210 patients with a single infarct and 150 with multiple infarcts, as well as in 101 non-stroke control patients. An ulcer was defined as a crater on the plaque ≥2.0 mm in depth and width. Results An ulcerated plaque was identified in 10.6% of patients with stroke versus 2.0% of non-stroke patients, showing a 5.11-fold higher frequency in patients with stroke (95% CI 1.51 to 31.96) after adjustment for age and sex. After multivariate adjustment for clinical and ultrasonographic features, multiple-infarct patients had a 7.61-fold higher risk (95% CI 1.99 to 50.43) of having an ulcer than control patients and a 3.32-fold higher risk (95% CI 1.61 to 7.18) of having an ulcer than single-infarct patients. Diabetes mellitus and drinking habit were independently related to the presence of ulcerated plaque in patients with stroke. Conclusions Ulcerated plaque in the aortic arch was associated with the development of ischaemic stroke, especially multiple brain infarcts, probably involving, at least in part, an embolic mechanism.