Improvement and Aggravation of Spontaneous Unruptured Vertebral Artery Dissection.

BACKGROUND: Intracranial vertebral artery dissection (VAD) is a well-recognized cause of stroke in young and middle-aged individuals, especially in Asian populations. However, a long-term natural course remains unclear. We investigated the long-term time course of VAD using imaging findings to examine the rate and predisposing factors for improvement. METHODS: We registered 56 consecutive patients (40 males; mean age, 51.8 ± 10.7 years) with acute spontaneous VAD and retrospectively investigated neuroimaging and clinical course within 1 month and at 3 months ± 2 weeks, 6 months ± 2 weeks, and 12 months ± 2 weeks after onset to ascertain predisposing factors and time course for improvement. RESULTS: The most common presenting symptoms were headache and/or posterior neck pain, seen in 41 patients (73%). Magnetic resonance imaging showed brainstem and/or cerebellum infarction in only 32 patients (57%). Of the 56 VADs, 16 (28%) presented with pearl and string sign, 5 (9%) with pearl sign, 15 (27%) with string sign, and 20 (36%) with occlusion sign. VAD occurred on the dominant side in 20 patients and on the nondominant side in the other 36 patients. The pearl and string sign was more frequently noted on the dominant side than on the nondominant side (50 vs. 17%, p = 0.008). On the other hand, occlusion occurred more often on the nondominant side than on the dominant side (47 vs. 15%, p = 0.016). Furthermore, the pearl and string sign was more frequently seen in the improvement group (41 vs. 15%, p = 0.028), whereas the occlusion sign was evident more frequently in the nonimprovement group (21 vs. 52%, p = 0.015). Follow-up neuroimaging evaluation was performed at 1 and 3 months in 91% each, and at 6 and 12 months in 82% each. VAD aggravation was identified within 1 month after onset in 14%, while VAD improvement was seen in 14, 38, 50, and 52% at each period, mainly within 6 months after onset. Older patients and current smoking were negatively associated with VAD improvement. CONCLUSIONS: VAD improvement primarily occurs within 6 months after onset, and VAD aggravation within 1 month. It seems that older patients and current smoking are negative predictors of VAD improvement as risk factors, and as image findings, the pearl and string sign is a positive predictor and occlusion a negative predictor.

Dura mater graft-associated Creutzfeldt-Jakob disease with 30-year incubation period.

Over 60% of all patients with dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) have been diagnosed in Japan. The incubation period has ranged from 1 to 30 years and the age at onset from 15 to 80 years. Here, we report a 77-year-old male Japanese autopsied dCJD case with the longest incubation period so far in Japan. He received a cadaveric dural graft at the right cranial convexity following a craniotomy for meningioma at the age of 46. At 30 years post-dural graft placement, disorientation was observed as an initial symptom of dCJD. He rapidly began to present with inconsistent speech, cognitive impairment and tremor of the left upper extremity. Occasional myoclonic jerks were predominantly observed on the left side. Brain MRI presented hyperintense signals on diffusion-weighted and T2-weighted images, at the right cerebral cortex. The most hyperintense lesion was located at the right parietal lobe, where the dura mater graft had been transplanted. Single-photon emission CT scan showed markedly decreased cerebral blood flow at the right parietal lobe. EEG revealed diffuse and slow activities with periodic sharp-wave complex discharges seen in the right parietal, temporal and occipital lobes. He died of pneumonia 9 months after onset. Brain pathology revealed non-plaque-type dCJD. Laterality of neuropathological changes, including spongiform change, neuronal loss, gliosis or PrP deposits, was not evident. Western blot analysis showed type 1 PrPCJD . Alzheimer-type pathology and PSP-like pathology were also observed.

A multicenter, prospective, observational study of warfarin-associated intracerebral hemorrhage: The SAMURAI-WAICH study.

BACKGROUND: Because patients with warfarin-associated intracerebral hemorrhage (WAICH) have a high risk of ongoing bleeding, disability, and death, urgent coagulopathy reversal should be considered. On the other hand, thromboembolism may occur with reversal or withholding of anticoagulant therapy. The current status of acute hemostatic treatments and clinical outcomes in WAICH patients was investigated. METHODS: WAICH patients admitted within 3 days of onset were prospectively enrolled in 10 stroke centers. Thromboembolic and hemorrhagic complications and functional outcomes were followed-up for one year. RESULTS: Of 50 WAICH patients (31 men, 73 ± 9 years old) enrolled, all stopped warfarin on admission. Elevated prothrombin time-international normalized ratios (PT-INR) were normalized in 43 (86%). Anticoagulant therapy was resumed with intravenous full-dose unfractionated heparin followed by warfarin in 9 (18%), intravenous low-dose unfractionated heparin followed by warfarin in 14 (28%) and warfarin alone in 14 (28%) at a median of 2.5 (IQR 1.25-9), 4 (2-5.5) and 6 (3-11) days after onset, respectively, after emergent admission. Onset-to-admission time (per 1-hour increase; OR 0.55, 95% CI 0.19-0.84) was inversely associated with hematoma expansion. Anticoagulant therapy was resumed with intravenous full-dose unfractionated heparin in 9 (18%), low-dose heparin in 14 (28%) and warfarin alone in 14 (28%) at a median of 2.5, 4 and 6 days after onset, respectively. During one-year follow-up (n=47), 11 thromboembolic and 6 hemorrhagic complications were documented. Twenty four patients showed unfavorable outcomes, corresponding to a modified Rankin Scale score of 4-6. Thromboembolic complications (OR, 10.62; 95% CI, 1.05-227.85), as well as advanced age (per 1 year; OR, 1.27; 95% CI, 1.10-1.61) and higher National Institutes of Health Stroke Scale (NIHSS) score (per 1 point; OR, 1.24; 95% CI 1.07-1.55), were independently associated with unfavorable outcome. CONCLUSIONS: PT-INR normalization on admission and early anticoagulant resumption were common in WAICH patients. Thromboembolic complications were independently associated with unfavorable outcome.

Increase in the Size of an Intracardiac Thrombus during Dabigatran Therapy (110 mg b.i.d.) in an Acute Cardioembolic Stroke Patient.

We report a case of atrial fibrillation in a patient in whom a mobile thrombus in the left atrial appendage increased in size after low-dose dabigatran therapy. A 74-year-old man was admitted to our hospital because of sudden onset of right hemiplasia and dysarthria. On admission, his National Institutes of Health Stroke Scale score was three. Axial diffusion-weighted magnetic resonance images and magnetic resonance angiography images showed hyperintense signals in the left front-parietal cerebral cortex without any intracranial stenotic lesions, and acute cardioembolic stroke associated with nonvalvular atrial fibrillation was diagnosed. Transesophageal echocardiography revealed a mobile thrombosis (1.0 × 2.2 cm) in the left atrial appendage, and dabigatran therapy (110 mg b.i.d.) was initiated to prevent stroke recurrence. Transesophageal echocardiography performed 6 days later revealed that the size of the thrombus had increased to 1.5 × 3.0 cm. Medication was changed to warfarin, and the thrombosis subsequently decreased in size. The patient did not have a recurrent stroke and was discharged with a National Institutes of Health Stroke Scale score of zero. This case demonstrates that low-dose dabigatran may not be effective in reducing the size of a thrombus.

Effects of sex difference on clinical features of acute ischemic stroke in Japan.

BACKGROUND: Sex differences in stroke characteristics and outcomes have been inconsistent. The goal of this study was to determine the influence of sex on underlying patient characteristics, stroke subtypes and conditions, and outcomes after ischemic stroke from a nationwide registration study. METHODS: A total of 33,953 patients with acute ischemic stroke, including 13,323 women, were registered in a multicenter, hospital-based registration study based on a computerized database from 162 Japanese institutes (the Japan Standard Stroke Registry Study) between January 2000 and November 2007. RESULTS: Women were significantly older than men at stroke onset (75.0 ± 11.7 v 69.3 ± 11.4 years; P < .0001). After age adjustment, women more frequently had cardioembolic events (odds ratio [OR] 1.090; 95% confidence interval [95% CI] 1.036-1.146; P = .0009) and other strokes (OR 1.177; 95% CI 1.079-1.284; P = .0003) and were more hypertensive (OR 1.056; 95% CI 1.006-1.108; P = .0267) and more dyslipidemic (OR 1.301; 95% CI 1.234-1.373; P < .0001) than men. After multivariate adjustment, onset-to-arrival time was longer (ß = 0.0554; P = .026), the initial National Institutes of Health Stroke Scale score was higher (ß = 0.1565; P < .001), and the duration of hospitalization was longer (ß = 0.035; P = .010) in women than in men. At hospital discharge, women less commonly had a modified Rankin Scale (mRS) score of 0 to 1 (OR 0.802; 95% CI 0.741-0.868; P < .0001) and more commonly had a mRS score of 4 to 6 (OR 1.410; 95% CI 1.293-1.537; P < .0001) than men. CONCLUSIONS: Women developed more severe strokes than men in Japan. After multivariate adjustment for initial severity and other characteristics, acute care hospital stays were longer and stroke outcomes at discharge were worse in women than in men.

Intravenous alteplase at 0.6 mg/kg for acute stroke patients with basilar artery occlusion: the stroke acute management with urgent risk factor assessment and improvement (SAMURAI) Recombinant tissue plasminogen activator registry.

BACKGROUND: The therapeutic efficacy of low-dose intravenous alteplase (0.6 mg/kg) for basilar artery occlusion (BAO) remains unknown. METHODS: BAO patients enrolled from the Japanese multicenter registry involving 600 stroke patients treated with the low-dose intravenous alteplase were studied. RESULTS: Twenty-five patients had BAO (8 women ranging from 32-92 years of age; mean baseline National Institutes of Health Stroke Scale [NIHSS] score 16). The stroke subtype was cardioembolic in 15 patients and atherothrombotic in 4 patients. BAO was recanalized during hospitalization in 18 (78%) of 23 patients undergoing follow-up angiography. Within the initial 24 hours, 14 patients (56%) had a ≥ 8-point decrease in the NIHSS score, being more common than 267 patients with middle cerebral artery occlusion (MCO) from the same registry (odds ratio [OR] 2.50; 95% confidence interval [CI] 1.06-5.97) after adjustment by sex, age, and baseline NIHSS score. In addition, 4 patients (16%) had a ≥ 4-point increase in the score, being marginally more common than MCO patients (OR 3.13; 95% CI 0.81-10.25). Symptomatic intracranial hemorrhage within the initial 36 hours (8% v 5%), independence at 3 months (modified Rankin Scale score ≤ 2, 48% v 52%), and mortality at 3 months (4% v 6%) were similar when comparing BAO and MCO patients. When compared with previous studies of BAO, vital and functional outcomes at 3 months were relatively better in our study. CONCLUSIONS: The use of low-dose alteplase resulted in similar outcomes when comparing acute BAO and MCO patients.

Nationwide survey of neuro-specialists' opinions on anticoagulant therapy after intracerebral hemorrhage in patients with atrial fibrillation.

PURPOSE: A nationwide survey was conducted regarding anticoagulant therapy in patients with acute intracerebral hemorrhage (ICH) on warfarin with nonvalvular atrial fibrillation (NVAF). METHODS: A questionnaire on standard therapeutic strategy for warfarin-related ICH in patients with NVAF was mailed to 416 institutes. RESULTS: A total of 329 physicians (79%) responded with a completed questionnaire. On admission, all respondents stopped warfarin medication and 94% normalized the international normalized ratio (INR) mainly by Vitamin K (63%), followed by fresh frozen plasma (20%), and prothrombin complex concentrate (10%). Afterwards, 91% of the respondents restarted anticoagulation and 3% used antiplatelet for prevention of thromboembolism, but the remaining 6% disagreed with restarting antithrombotic therapy. As contraindications for resuming anticoagulation, recurrent ICH (59%) and poor functional condition (59%) were often chosen. Of those who restarted anticoagulation, the timing was within 4 days in 7%, 5 to 7 days in 21%, 8 to 14 days in 25%, 15 to 28 days in 28% and 29 days or later in 18%. The major key finding on follow-up CT to restart anticoagulation was the absorption tendency of hematomas (47%). When restarting anticoagulation, 76% of the respondents used warfarin alone and 20% used either unfractionated heparin plus warfarin or heparin alone. CONCLUSION: A large majority of respondents responsible for ICH management stopped oral warfarin medication and normalized INR on admission, and restarted anticoagulation after acute ICH in patients with NVAF. However, the strategies to normalize INR and to restart anticoagulant therapy varied greatly and depended on each individual physician's decision.

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 (ρ=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 [ß] 0.061, P<0.001) and cardioembolic stroke (ß 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.

CHADS2 score is associated with 3-month clinical outcomes after intravenous rt-PA therapy in stroke patients with atrial fibrillation: SAMURAI rt-PA Registry.

PURPOSE: The aim of this study was to examine whether CHADS(2) score is associated with clinical outcomes following recombinant tissue type plasminogen activator (rt-PA) therapy in stroke patients with atrial fibrillation (AF). METHODS: We studied 218 consecutive stroke patients with AF [126 men, mean age 74.2 (SD 9.6) years] who received intravenous rt-PA therapy. CHADS(2) score was calculated as follows: 2 points for prior ischemic stroke and 1 point for each of the following: age≥75 years, hypertension, diabetes, and congestive heart failure. RESULTS: Congestive heart failure was documented in 23 patients, hypertension in 138, age≥75 years in 116, diabetes in 35, and prior stroke in 35. The distribution of each CHADS(2) score was: score of 0, 16.1% of patients; 1, 30.3%; 2, 29.4%; and 3 to 5, 24.3%. The median initial NIHSS score for each CHADS(2) category was 12 (IQR 8-17), 16 (10-20), 14.5 (10-20.75), and 16 (11-21), respectively (p=0.168). Symptomatic ICH within the initial 36 h was found in 2.9%, 4.6%, 6.3%, and 0% of patients with each CHADS(2) category, respectively. Cardiovascular events within 3 months occurred in 0%, 0%, 7.8% and 5.7%, respectively. Percentage of patients with chronic independence at 3 months corresponding to modified Rankin Scale≤2 was 57.1%, 45.5%, 31.3%, and 28.3%, respectively. Adjusted CHADS(2) score was inversely associated with chronic independence (OR 0.72, 95% CI 0.55-0.93). CONCLUSION: Lower CHADS(2) score was associated with chronic independence at 3 months after intravenous rt-PA therapy in stroke patients with AF.