Dual Antiplatelet Therapy With Cilostazol for Secondary Prevention in Lacunar Stroke: Subanalysis of the CSPS.com Trial.

BACKGROUND: The effectiveness of long-term dual antiplatelet therapy (DAPT) to prevent recurrent strokes in patients with lacunar stroke remains unclarified. Therefore, this study aimed to compare and to elucidate the safety and effectiveness of DAPT and single antiplatelet therapy (SAPT) in preventing recurrence in chronic lacunar stroke. METHODS: CSPS.com (Cilostazol Stroke Prevention Study for Antiplatelet Combination) was a prospective, multicenter, randomized controlled trial. In this prespecified subanalysis, 925 patients (mean age, 69.5 years; 69.4% men) with lacunar stroke were selected from 1884 patients with high-risk noncardioembolic stroke, enrolled in the CSPS.com trial after 8 to 180 days following stroke. Patients were randomly assigned to receive either SAPT or DAPT using cilostazol and were followed for 0.5 to 3.5 years. The primary efficacy outcome was the first recurrence of ischemic stroke. The safety outcomes were severe or life-threatening bleeding. RESULTS: The DAPT group receiving cilostazol and either aspirin or clopidogrel and SAPT group receiving aspirin or clopidogrel alone comprised 464 (50.2%) and 461 (49.8%) patients, respectively. Ischemic stroke occurred in 12 of 464 patients (1.84 per 100 patient-years) in the DAPT group and 31 of 461 patients (4.42 per 100 patient-years) in the SAPT group, during follow-up. After adjusting for multiple potential confounding factors, ischemic stroke risk was significantly lower in the DAPT group than in the SAPT group (hazard ratio, 0.43 [95% CI, 0.22-0.84]). The rate of severe or life-threatening hemorrhage did not differ significantly between the groups (2 patients [0.31 per 100 patient-years] versus 6 patients [0.86 per 100 patient-years] in the DAPT and SAPT groups, respectively; hazard ratio, 0.36 [95% CI, 0.07-1.81]). CONCLUSIONS: In patients with lacunar stroke, DAPT using cilostazol had significant benefits in reducing recurrent ischemic stroke incidence compared with SAPT without increasing the risk of severe or life-threatening bleeding. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000012180.

Dual Antiplatelet Therapy Using Cilostazol With Aspirin or Clopidogrel: Subanalysis of the CSPS.com Trial.

Background and Purpose: Although dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduces the recurrence of ischemic stroke while significantly increasing the bleeding events compared with monotherapy, the CSPS.com trial (Cilostazol Stroke Prevention Study combination) showed that DAPT using cilostazol was more effective without the bleeding risk. In the CSPS.com trial, aspirin or clopidogrel was used as the underlying antiplatelet drug. The effectiveness and safety of each combination were examined and clarified. Methods: In the CSPS.com trial, a multicenter, open-label, randomized controlled study, patients with high-risk, noncardioembolic ischemic stroke 8 to 180 days after onset treated with aspirin or clopidogrel alone at the discretion of the physician in charge were recruited. Patients were randomly assigned to receive either monotherapy or DAPT using cilostazol and followed for 0.5 to 3.5 years. The primary efficacy outcome was first recurrence of ischemic stroke. The safety outcome was severe or life-threatening bleeding. The analysis was based on the underlying antiplatelet agents. Results: A total of 763 patients taking aspirin and 1116 taking clopidogrel were included in the intention-to-treat analysis. Although the clopidogrel group had more risk factors than the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the 2 groups. In the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the DAPT group and the aspirin-monotherapy group. In the clopidogrel group, the primary end point occurred at a rate of 2.31 per 100 patient-years in the DAPT group and 5.19 per 100 patient-years in the clopidogrel-monotherapy group (hazard ratio, 0.447 [95% CI, 0.258­0.774]). Safety outcome did not differ significantly between groups (0.51 per 100 patient-years versus 0.71 per 100 patient-years, respectively; hazard ratio, 0.730 [95% CI, 0.206­2.588]). Conclusions: The combination of cilostazol and clopidogrel significantly reduced the recurrence of ischemic stroke without increasing the bleeding risk in noncardioembolic, high-risk patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000012180.

Evaluation of Risk Factors for Major Amputation in Patients With Diabetes and Peripheral Artery Disease Receiving Antiplatelet Therapy　- Post Hoc Analysis of a Prospective Observational Multicenter Cohort Study (SEASON).

BACKGROUND: Guidelines for peripheral arterial disease (PAD) recommend long-term antiplatelet therapy in symptomatic patients to reduce cardiovascular morbidity and mortality risk. Although diabetes is a known risk factor for PAD, PAD has been undertreated in these patients. This study aimed to evaluate risk factors for major amputation in patients with diabetes undergoing antiplatelet therapy for PAD.Methods and Results:This retrospective analysis of a 2-year observational cohort study (1,745 clinics in Japan, September 2009-2013) evaluated predictors of amputation in patients with diabetes undergoing antiplatelet therapy for PAD. Among 4,016 eligible patients, 52 had an amputation during follow-up. Amputation risk (Cox regression analysis) was predicted at baseline by history of lower extremity revascularization/amputation (hazard ratio [HR]: 2.92; 95% confidence interval [CI]: 1.39, 6.14), chronic kidney disease (HR: 4.19; 95% CI: 1.95, 8.97), and comorbid cerebrovascular and heart disease (HR: 3.32; 95% CI: 1.19, 9.30), and was unaffected by choice of oral antiplatelet therapy. In patients with PAD and diabetes, amputation event rate was highest for those with ankle-brachial pressure index (ABI) <0.40 and progressively decreased at higher ABI cut-offs. CONCLUSIONS: These findings inform real-world understanding of PAD in diabetic patients receiving antiplatelet therapy in Japan, and showed that ABI <0.4 was the strongest risk factor for amputation.

Baseline Characterization of Japanese Peripheral Arterial Disease Patients　- Analysis of Surveillance of Cardiovascular Events in Antiplatelet-Treated Arteriosclerosis Obliterans Patients in Japan (SEASON).

BACKGROUND: Despite mounting evidence of increased cardiovascular events in patients with peripheral arterial disease (PAD), the overall incidence of cardiovascular events in PAD patients has not been fully clarified in Japan. The prospective Surveillance of cardiovascular Events in Antiplatelet-treated arterioSclerosis Obliterans patients in JapaN (SEASON) is a prospective observational multicenter study and here we report the baseline clinical characteristics, including atherosclerosis risk factor prevalence, in PAD patients treated with antiplatelet agents. METHODS AND RESULTS: The SEASON registry enrolled 11,375 patients in 1,745 institutions and the data for 10,322 patients were analyzed. At baseline, the average age was 73.8±9.9 years, 60.0% were male and 83.9% were in Fontaine stage I or II. They had arteriosclerosis risk factors, such as current smoking (16.2%), hypertension (61.5%), diabetes mellitus (38.3%) and dyslipidemia (38.8%). There were complications including heart disease (29.7%), cerebrovascular disease (17.1%) and chronic kidney disease (14.3%). A subpopulation analysis revealed that the proportions of patients with risk factors were high in patients with lower ankle-brachial pressure index value. CONCLUSIONS: The baseline characteristics of the SEASON population demonstrate that real-world PAD patients have cardiovascular risk factors and comorbidities next to definite PAD patients. Further analysis of this database will contribute to understanding the real-world situation of PAD patients receiving antiplatelet therapy in Japan. (Circ J 2016; 80: 712-721).

Detectability of ischemic lesions on diffusion-weighted imaging is biphasic after transient ischemic attack.

BACKGROUND: Experimental studies of transient focal ischemia indicate biphasic detectability of lesions by diffusion-weighted imaging (DWI); poorly detectable phase exists at 1-12 hours after reperfusion. The present study aimed to clarify whether poorly detectable phase also exists in DWI of transient ischemic attack (TIA) patients. METHODS: A retrospective study was conducted in 144 consecutive TIA patients who underwent magnetic resonance imaging (MRI) within 2 weeks after carotid TIA. Patients were classified into 9 groups according to time from disappearance of TIA symptoms to DWI: intraischemic period, 0-1 hour, 1-12 hours, 12-24 hours, 1-2 days, 2-3 days, 3-7 days, 7-10 days, and 10-14 days after the end of TIA. RESULTS: Lesions were detected in 33 of 144 patients (22.9%). The frequency of positive lesions was 20% in the intraischemic period and 30.8% at 0-1 hour after the end of TIA; it markedly decreased to 8.7% at 1-12 hours after end of TIA. Thereafter, it increased to 21.7%, 30.8%, 36.4%, 37.0%, 38.5%, and 30% at 12-24 hours, 1-2 days, 2-3 days, 3-7 days, 7-10 days, and 10-14 days after the end of TIA, respectively. In 7 patients, MRI was repeated twice, at 1-12 hours and then at 5-13 days after the end of TIA. Lesions were never detected on the first MRI but were clearly demonstrated in 4 of 7 patients on the second MRI. CONCLUSIONS: The detectability of ischemic lesions may be biphasic after TIA as indicated by experimental studies.

Effect of a Low-Intensity Pulsed Ultrasound Device, SX-1001, on Clinical Symptoms in Buerger Disease With Limb Ischemia.

Buerger disease is a rare disease of unknown etiology and cannot be treated by bypass surgery or percutaneous re-endovascularization. Although the need for effective limb ischemia prevention strategies is increasingly being recognized, effective preventative strategies are insufficient. The aim of this study using a new pulsed ultrasound device, SX-1001, is to determine whether treatment using SX-1001 can mitigate rest pain and improve blood supply to ischemic legs in patients with Buerger disease. This study is a multicenter, double-blinded, parallel randomized clinical trial testing the efficacy and safety of SX-1001. Treatment using SX-1001 is expected to result in reduction of the visual analog scale score for pain in Buerger disease patients who have Fontaine stage III. A total of 44 patients from 20 hospitals in Japan will be enrolled. The primary endpoint of the trial is a change in rest pain intensity on the visual analog scale score from baseline to 24 weeks. This trial will be the first to show the safety and efficacy of low-intensity pulsed ultrasound using SX-1001 for clinical symptoms in patients with Buerger disease. Low-intensity pulsed ultrasound may be a new therapy for limb ischemia. Ethical approval has been obtained from each of the participating institutes. Study findings will be disseminated through peer-reviewed journals and at scientific conferences.This study is registered at UMIN Clinical Trial Registry (UMIN000014757).

Factors contributing to mortality and morbidity in pregnancy-associated intracerebral hemorrhage in Japan.

AIM: The aim of this study was to analyze the causes and outcomes for intracerebral hemorrhage (ICH) occurring during pregnancy and postnatally. MATERIAL AND METHODS: A nationwide study of pregnancy-related ICH in Japan was performed. We contacted 1582 facilities to identify women with ICH in pregnancy or postnatally between 1 January 2006 and 31 December 2006. A total of 1012 facilities (70%) responded with completed questionnaires. Risk factors for ICH, neurological features, onset to diagnosis time (O-D time), and obstetric data were recorded. RESULTS: Thirty-eight cases of pregnancy-associated ICH were identified, corresponding to 3.5 per 100 000 deliveries. There were seven maternal deaths, giving a case mortality rate of 18.4%. Pre-eclampsia was identified in 10 cases (26.3%) and hemolysis elevated liver enzymes and low platelet count (HELLP) syndrome was present in five. There were four cases (10.5%) with Moyamoya disease and seven (18.4%) with arteriovenous malformation. HELLP syndrome and moderately or severely disturbed consciousness at disease onset were significantly associated with a poor outcome (modified Rankin Scale ≥3). Pre-eclampsia, HELLP syndrome and O-D time >3 h were significantly associated with maternal mortality. CONCLUSION: Early diagnosis may prevent maternal death, even in severe cases of pregnancy-related ICH. However, maternal-fetal care centers do not always have full-time neurosurgeons or diagnostic imaging tools suitable for diagnosis of ICH. Thus, a network should be established between maternity centers and neurosurgery departments with computed tomography or magnetic resonance imaging available at all times. We recommend transferal of pregnant women with neurological symptoms to a regional facility that is equipped to treat such patients.

Estimation of stroke etiology from lesion patterns on diffusion-weighted magnetic resonance imaging in patients with carotid artery occlusive disease.

BACKGROUND: Various mechanisms can be considered in ischemic stroke with internal carotid artery (ICA) occlusive diseases. We clarified the etiologic mechanisms from lesion patterns on diffusion-weighted imaging (DWI). METHODS: One hundred and twenty consecutive ischemic stroke patients with ipsilateral ICA occlusive diseases were enrolled and classified into 3 groups according to the size of DWI lesions: group A, massive; group B, moderate-to-large; and group C, small. Group C was divided into 3 subgroups according to the number of lesions: C1, 1-3; C2, 4-9; and C3, 10 or more. The relationship between the DWI findings and stroke subtypes according to the TOAST classification was investigated. RESULTS: Cardioembolism was significantly more common in groups A and B than in group C, while large-artery atherosclerosis (LAA) was more frequent in group C than in groups A and B. In group A, cardioembolism accounted for 32%, while LAA was not observed. Statistical analyses showed trends toward a higher frequency of LAA in groups C2 and C3 than in group C1. CONCLUSIONS: Mechanisms of acute stroke in ICA diseases can be simply assessed from the lesion size and number, which may be useful in considering acute therapeutic strategies.

High plasma D-dimer is a marker of deep vein thrombosis in acute stroke.

This study investigated whether plasma D-dimer level is useful for detection of deep vein thrombosis (DVT) in patients with acute stroke. A total of 133 patients hospitalized within 3 days after stroke onset underwent duplex venous ultrasonographic examination of the lower limbs and repeated measurements of plasma D-dimer level. DVT was detected in 36 of 100 patients with ischemic stroke and in 25 of 33 patients with intracerebral hemorrhage (ICH) (76%; P < .001). Plasma D-dimer level on admission (7.5 ± 10.7 µg/mL vs 3.7 ± 10.1 µg/mL; P = .040) and its maximum level before the ultrasonographic examination (29.1 ± 48.7 µg/mL vs 5.5 ± 11.0 µg/mL; P < .001) were higher in the patients with DVT compared with those without DVT. On multivariate logistic regression analysis, the maximum D-dimer level was independently related to the identification of DVT (odds ratio [OR] 1.05; 95% confidence interval [CI], 1.00-1.09 per 1-µg/mL increase; P = .045), but the admission D-dimer level was not when it was included instead of the maximum D-dimer level. In addition, female sex (OR, 4.99), ICH (OR, 5.20), high Wells clinical score (OR, 2.40 per 1-point increase), and low protein level (OR, 0.21 per 1-g/dL increase) were independently related to the identification of DVT. The optimum cutoff value of the maximum D-dimer level for positive DVT was 5.5 µg/mL (sensitivity, 89%; specificity, 82%). Our findings suggest that high plasma D-dimer level during the course of acute stroke can help detect DVT on duplex venous ultrasonography.

Prospective multicentre cohort study of heparin-induced thrombocytopenia in acute ischaemic stroke patients.

Acute ischaemic stroke patients sometimes receive heparin for treatment and/or prophylaxis of thromboembolic complications. This study was designed to elucidate the incidence and clinical features of heparin-induced thrombocytopenia (HIT) in acute stroke patients treated with heparin. We conducted a prospective multicentre cohort study of 267 patients who were admitted to three stroke centres within 7 d after stroke onset. We examined clinical data until discharge and collected blood samples on days 1 and 14 of hospitalization to test anti-platelet factor 4/heparin antibodies (anti-PF4/H Abs) using an enzyme-linked immunosorbent assay (ELISA); platelet-activating antibodies were identified by serotonin-release assay (SRA). Patients with a 4Ts score ≥4 points, positive-ELISA, and positive-SRA were diagnosed as definite HIT. Heparin was administered to 172 patients (64·4%: heparin group). Anti-PF4/H Abs were detected by ELISA in 22 cases (12·8%) in the heparin group. Seven patients had 4Ts ≥ 4 points. Among them, three patients (1·7% overall) were also positive by both ELISA and SRA. National Institutes of Health Stroke Scale score on admission was high (range, 16-23) and in-hospital mortality was very high (66·7%) in definite HIT patients. In this study, the incidence of definite HIT in acute ischaemic stroke patients treated with heparin was 1·7% (95% confidence interval: 0·4-5·0). The clinical severity and outcome of definite HIT were unfavourable.

Effect of prothrombin complex concentrate on hematoma enlargement and clinical outcome in patients with anticoagulant-associated intracerebral hemorrhage.

BACKGROUND: The present study was carried out to determine the effect of prothrombin complex concentrate (PCC) on hematoma enlargement (HE) and the early clinical outcome of intracerebral hemorrhage (ICH) patients on long-term warfarin treatment. METHODS: The medical records and computed tomography (CT) images of 50 consecutive ICH patients on long-term warfarin treatment (35 men, 15 women; 69 ± 12 years old) were reviewed. International normalized ratio (INR) values, frequency of HE and clinical outcome were compared between patients treated with and without PCC. RESULTS: INR values on admission were above 2.0 in 37 patients, of whom 19 were given PCC (PCC group) and 18 were not given PCC (control group). In these 37 patients, the frequency of HE (p = 0.017), the number of patients with a poor clinical outcome (modified Rankin Scale score ≥3 at 30 days or at discharge; p = 0.045) and in-hospital mortality (p = 0.042) were significantly higher in the control than in the PCC group. On multivariate logistic regression analysis with adjustment, PCC administration was independently associated (odds ratio 0.03, 95% confidence interval 0.00-0.63; p = 0.023) with a reduction in poor clinical outcome in ICH patients whose INR values were >2.0 on admission. CONCLUSIONS: Immediate INR reversal with PCC may prevent HE and subsequent poor outcome.

Carotid duplex ultrasonography can predict outcome of intravenous alteplase therapy for hyperacute stroke.

We evaluated whether carotid duplex ultrasonography (US) can help predict the safety and efficacy of treating hyperacute stroke with intravenous (IV) tissue plasminogen activator (alteplase) therapy. Consecutive patients with stroke were assigned to the carotid artery occlusion (CO) group or the other (non-CO) group according to US findings before or immediately after receiving IV alteplase. Effectiveness and safety outcomes included early neurologic improvement, defined as a reduction in a National Institutes of Health Stroke Scale (NIHSS) score of ≥4 points within the initial 24 hours after stroke onset; completely independent routine activity, defined as a modified Rankin Scale score of ≤1 at day 90 after stroke onset; symptomatic intracranial hemorrhage (ICH) occurring within 36 hours after stroke onset; and any ICH. We enrolled 127 patients (27 in the CO group and 100 in the non-CO group) with a median baseline NIHSS score of 13 (range, 4-30). The CO group had a higher baseline NIHSS score (median, 18 vs 12; P=.005). After multivariate adjustment, the CO group was inversely associated with early improvement (odds ratio [OR]=0.26; 95% confidence interval [CI]=0.09-0.72) and independence at day 90 (OR=0.23; 95% CI=0.05-0.73) and positively associated with any ICH (OR=3.11; 95% CI=1.23-8.48). Our findings indicate that CO identified by US in the emergency clinical setting is an independent predictor of unfavorable outcome and ICH following IV alteplase therapy.

Dual Antiplatelet Therapy Using Cilostazol in Patients With Stroke and Intracranial Arterial Stenosis.

Background Long-term benefit of dual antiplatelet therapy (DAPT) over single antiplatelet therapy (SAPT) for the prevention of recurrent stroke has not been established in patients with intracranial arterial stenosis. We compared the efficacy and safety of DAPT with cilostazol and clopidogrel or aspirin to those of SAPT with clopidogrel or aspirin in patients with intracranial arterial stenosis, who were recruited to the Cilostazol Stroke Prevention Study for Antiplatelet Combination trial, a randomized controlled trial in high-risk Japanese patients with ischemic stroke. Methods and Results We compared the vascular and hemorrhagic events between DAPT and SAPT in patients with ischemic stroke and symptomatic or asymptomatic intracranial arterial stenosis of at least 50% in a major intracranial artery. Patients were placed in two groups: 275 were assigned to receive DAPT and 272 patients SAPT. The risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.23-0.95); and composite of stroke, myocardial infarction, and vascular death (HR, 0.48; 95% CI, 0.26-0.91) were lower in DAPT than SAPT, whereas the risk of severe or life-threatening bleeding (HR, 0.72; 95% CI, 0.12-4.30) did not differ between the 2 treatment groups. Conclusions DAPT using cilostazol was superior to SAPT with clopidogrel or aspirin for the prevention of recurrent stroke and vascular events without increasing bleeding risk among patients with intracranial arterial stenosis after stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370.

Reduced tongue pressure against the hard palate on the paralyzed side during swallowing predicts Dysphagia in patients with acute stroke.

BACKGROUND AND PURPOSE: Dysphagia is important for prognosis in patients with stroke because this condition can cause aspiration pneumonia or nutritional deficits. The present study investigated the relationship between tongue motor deficits and dysphagia in patients with acute stroke. METHODS: Maximal tongue pressure on the hard palate when swallowing 5 mL of water was measured using a T-shaped sensor sheet with 5 measuring points in 33 dysphagic and 31 nondysphagic patients with acute stroke. Maximum tongue pressures at each measuring point were compared between dysphagic and nondysphagic groups and between paralyzed and nonparalyzed sides. RESULTS: Tongue pressure at each measuring point was significantly smaller in dysphagic patients than in nondysphagic patients with the largest significant difference on the paralyzed side. The magnitude of tongue pressure to predict dysphagia was calculated as 4.6 kPa on the paralyzed side, offering 71.4% sensitivity and 72.3% specificity. CONCLUSIONS: Reduced tongue pressure on the paralyzed side may predict dysphagia in patients with acute stroke.

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.

Symptom progression or fluctuation in transient ischemic attack patients predicts subsequent stroke.

BACKGROUND: The aim of this study was to investigate whether progression or fluctuation of transient ischemic attack (TIA) symptoms is a predictor of subsequent stroke. METHODS: We prospectively analyzed 113 consecutive patients admitted with a diagnosis of classical TIA with symptom duration of less than 24 h. We assessed the background characteristics, TIA symptoms, attack characteristics, results of in-hospital examinations, and prescription of antithrombotic agents on discharge for each patient. We then analyzed the factors related to progression or fluctuation of TIA symptoms. RESULTS: Of the 113 patients, 35 (31.0%) exhibited symptom progression or fluctuation. Subsequent stroke occurred in 12 (10.6%) patients within 180 days. Symptom progression or fluctuation was significantly related to the TIA symptoms of speech disturbance, hemiparesis, and monoparesis, and were also related to subsequent stroke occurrence within 90 days (29 vs. 3%, p = 0.004) and 180 days (23 vs. 5%, p = 0.008). In a logistic regression model analysis, symptom progression or fluctuation was a significant predictor of subsequent stroke within 90 days (odds ratio = 7.65, 95% CI 1.27-46.06) and 180 days (odds ratio = 4.44, 95% CI 1.08-18.13), independently of other predictors demonstrated in previous studies. CONCLUSIONS: Progression or fluctuation of TIA symptoms may be an important predictor of subsequent stroke. A detailed interview about the characteristics of each attack is also indispensable for the provision of appropriate care to TIA patients.

Enlargement of acute intracerebral hematomas in patients on long-term warfarin treatment.

BACKGROUND: The relationship between warfarin administration and the frequent development of enlarged hematomas in patients with acute intracerebral hemorrhage (ICH) is controversial. The present study was carried out to examine this issue. METHODS: This study reviewed 41 patients with nontraumatic ICH within 24 h after stroke onset from 1999 to 2003 who received long-term warfarin treatment (29 men and 12 women, 70 +/- 12 years old) and 323 patients who had not been on warfarin (177 men and 146 women, 66 +/- 13 years old). The hematoma volume (HV) on admission, final HV, frequency of hematoma enlargement (HE) and other background characteristics were investigated. RESULTS: Both the HV on admission (p = 0.031) and final HV (p = 0.001) were larger in patients on warfarin than in those not receiving warfarin. HE occurred more frequently (p < 0.001), and mortality at 30 days or at discharge was higher (p = 0.003) in the warfarin group than in the control group. A multivariate adjusted logistic regression analysis showed that warfarin treatment (OR = 5.75, 95% CI = 2.41-13.8, p < 0.001), liver disease (OR = 2.59, 95% CI = 1.12-5.99, p = 0.026), and the National Institutes of Health Stroke Scale score (OR = 1.10, 95% CI = 1.04-1.15, p < 0.001, per 1-score increase) on admission were independently related to HE. CONCLUSIONS: Acute ICH in patients on long-term warfarin treatment appears to be associated with HE.

Isolated anterior cerebral artery territory infarction: dissection as an etiological mechanism.

BACKGROUND: Intracranial arterial lesions are important causes of ischemic stroke, particularly in the Asian population. Of the intracranial lesions, the etiology of isolated anterior cerebral artery (ACA) territory infarction is not fully elucidated. The purpose of this study was to determine the etiological and clinical characteristics of patients with isolated ACA territory infarction, especially those with ACA dissection. METHODS: Of 3,115 consecutive patients with acute ischemic stroke, 42 patients (1.3%, 30 men, 38-88 years old) having an isolated ACA territory infarction were studied. Infarcts were principally verified by diffusion-weighted MRI, and vascular lesions were identified by MRA, CTA, or digital subtraction angiography. Three-dimensional rotational angiography was performed if needed. RESULTS: Eighteen patients (43%) were diagnosed as having ACA dissection. The stroke subtypes of the other 24 patients included cardioembolism for 6 patients and large-artery atherosclerosis for 8. Patients with dissection were younger (p < 0.001) and heavier (p = 0.026), less commonly had heart disease (p = 0.002) and previous stroke (p = 0.002), and had lower initial systolic blood pressure (p = 0.029) and lower levels of D-dimer (p = 0.041) than patients without dissection. Stroke onset more commonly followed physical exertion (p = 0.013) and headache (p = 0.041) in patients with dissection than in patients without dissection. At hospital discharge, the modified Rankin scale score was lower in patients with dissection than in patients without dissection (p = 0.005). CONCLUSIONS: Arterial dissection was the most common vascular lesion underlying an isolated ACA territory infarction in our Japanese cohort. Patients with ACA dissection had unique baseline characteristics and unique conditions at stroke onset.

Atheromatous plaques at the origin of the left subclavian artery in patients with ischemic stroke.

BACKGROUND: Atheromatous plaques of the aortic arch that extend to the origin of its branches may cause stroke. The frequency and clinical implications of plaque at the origin of the left subclavian artery (LSCA) in patients with recent ischemic stroke were investigated. METHODS: We studied 347 consecutive patients (223 men, 69 +/- 12 years) who developed symptomatic ischemic stroke and underwent transesophageal echocardiography (TEE). RESULTS: The origin of the LSCA was identified in 303 of 347 patients (87.3%). Plaque > or =1.0 mm was detected in 108 of the 303 patients (35.6%), ranging between 1.0 and 6.1 mm (median, 2.5 mm). Patients having thicker plaque (> or =2.5 mm) were older (p = 0.012) and more commonly took antiplatelets prior to stroke (p = 0.038) than patients with no plaque and those with thinner plaque (<2.5 mm). Of the aortic arch findings detected on TEE, maximum intima-media thickness (IMT) was the highest (p < 0.001) in patients with thicker plaque, and large plaque (> or =4.0 mm) (p = 0.017), ulcerative plaques (p < 0.001), and spontaneous echo contrasts (p = 0.001) were identified most commonly in patients with thicker plaque. The frequency of infarcts involving the posterior circulation was similar among the three groups. After multivariate adjustment, maximum IMT of the aortic arch was independently related to thicker plaque at the LSCA origin (OR = 1.24, 95% CI = 1.03-1.51, p = 0.024, per 1-mm increase). CONCLUSIONS: Atheromatous plaque at the origin of the LSCA was present in approximately one third of patients with a recent ischemic stroke. High IMT at the aortic arch was independently related to the presence of thick plaque at the LSCA origin. The present study does not support the concept that plaque at the LSCA origin may be associated with posterior circulation infarction.

Relationship between tongue pressure and dysphagia in stroke patients.

BACKGROUND: Although poststroke dysphagia is an important issue for determining prognosis, the pathophysiology of oral-phase dysphagia has yet to be clarified due to a lack of adequate devices and protocols. The present study investigated the relationships between swallowing pressure production by the tongue and dysphagia in stroke patients using a newly developed method of tongue pressure measurement with a sensor sheet system. METHODS: Subjects were 64 stroke patients, including 30 patients with dysphagia. A T-shaped sensor sheet with 5 measuring points was attached to the hard palate to record tongue pressure while swallowing 5 ml of water. The average maximal magnitude and incidence of abnormalities such as asynchronous and/or polyphasic patterns in tongue pressure waves in 5 locations were compared between patients with and without dysphagia. RESULTS: The average maximal tongue pressure was significantly smaller in patients with dysphagia than in those without dysphagia. Asynchronous and polyphasic patterns showed a sensitivity of 63 and 87%, and a specificity of 91 and 71%, respectively, for identifying patients with dysphagia. CONCLUSION: Tongue pressure production during swallowing appears closely related to poststroke dysphagia. Tongue pressure measurement appears useful for evaluating the pathophysiology of oral-phase dysphagia in stroke patients.