Increasing evidence points to a role for circulating endothelial progenitor cells, including populations of CD34- and CD133-positive cells present in peripheral blood, in maintenance of the ...vasculature and neovascularization. Immature populations, including CD34-positive cells, have been shown to contribute to vascular homeostasis, not only as a pool of endothelial progenitor cells but also as a source of growth/angiogenesis factors at ischemic loci. We hypothesized that diminished numbers of circulating immature cells might impair such physiological and reparative processes, potentially contributing to cerebrovascular dysfunction.
The level of circulating immature cells, CD34-, CD133-, CD117-, and CD135-positive cells, in patients with a history of atherothrombotic cerebral ischemic events was analyzed to assess possible correlations with the degree of carotid atherosclerosis and number of cerebral infarctions. There was a strong inverse correlation between numbers of circulating CD34- and CD133-positive cells and cerebral infarction. In contrast, there was no correlation between the degree of atherosclerosis and populations of circulating immature cells. Analysis of patients with cerebral artery occlusion revealed a significant positive correlation between circulating CD34- and CD133-positive cells and regional blood flow in areas of chronic hypoperfusion.
These results suggest a possible contribution of circulating CD34- and CD133-positive cells in maintenance of the cerebral circulation in settings of ischemic stress. Our data demonstrate the utility of a simple and precise method to quantify circulating CD34-positive cells, the latter providing a marker of cerebrovascular function.
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.
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.
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.
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.
Rationale and aims
Monotherapy with antiplatelet agents is only modestly effective in secondary prevention of ischemic stroke (IS), particularly in patients with multiple risk factors such as ...cervicocephalic arterial stenosis, diabetes, and hypertension. While dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduced IS recurrence, particularly in the early stages after IS, it increased the risk of bleeding. Compared with aspirin, cilostazol prevented IS recurrence without increasing the incidence of serious bleeds. In patients with intracranial arterial stenosis, no significant increase in bleeding events was observed for DAPT with cilostazol and aspirin, compared to that for aspirin monotherapy. DAPT involving cilostazol may therefore be safer than conventional DAPT. These findings prompted us to conduct the Cilostazol Stroke Prevention Study for Antiplatelet Combination (CSPS.com; ClinicalTrials.gov identifier: NCT01995370) to evaluate the safety and efficacy of DAPT involving cilostazol for secondary IS prevention, in comparison with that of antiplatelet monotherapy.
Design
The CSPS.com is a multicenter, randomized, open-label, parallel-group trial. A total of 4000 high-risk patients with noncardioembolic IS will be randomized 8–180 days after onset to receive aspirin or clopidogrel monotherapy, or DAPT with cilostazol and aspirin or clopidogrel for at least one-year.
Study outcomes
The primary outcome is IS recurrence. Secondary outcomes are composite occurrences of any stroke, death from any cause, myocardial infarction, vascular death, and other vascular events.
Discussion
The CSPS.com is expected to provide evidence indicating whether secondary IS prevention in high-risk patients can be improved by using DAPT involving cilostazol.
The aim of this study was to investigate whether progression or fluctuation of transient ischemic attack (TIA) symptoms is a predictor of subsequent stroke.
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.
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.
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.
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.
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.
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).
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.
Approximately one quarter of the acute ischemic stroke patients notice the event at awakening. Such patients with stroke at awakening are usually excluded from thrombolysis, since the time of stroke ...onset cannot be definitely identified. We compared the hyperacute CT findings of awakening stroke patients with those of stroke patients with known onset to assess whether the time of stroke onset is shortly before awakening.
Subjects were cardioembolic stroke patients who were consecutively admitted to our department within 3 h after the recognition of stroke during the period between January 2000 and March 2003. The patients were classified into three groups: group A with stroke of known onset, group B with stroke at awakening, and group C with stroke of unknown onset due to lack of a witness. The clinical and CT findings in each group were compared.
A total of 81 patients fulfilled the study criteria. There were 46 patients in group A, 17 patients in group B, and 18 patients in group C. There was no significant difference in CT findings between groups A and B. In group C, however, definite hypodense areas were more commonly found than in group A (56 vs. 0%; p<0.001) or in group B (56 vs. 11%; p=0.012).
Based on our CT findings, stroke at awakening seems to be developing shortly before in a large subset of patients, making them potential candidates for acute stroke therapies.
CYP2C9, a drug-metabolizing enzyme, converts the angiotensin II receptor blocker losartan to its active form, which is responsible for its antihypertensive effect. We resequenced CYP2C9 in 724 ...Japanese individuals, including 39 hypertensive patients under treatment with losartan. Of two novel missense mutations identified, the Arg132Gln variant showed a fivefold lower intrinsic clearance toward diclofenac when expressed in a baculovirus-insect cell system, while the Arg335Gln variant had no substantial effect. Several known missense variations were also found, and approximately 7% of the Japanese individuals (53 out of 724) carried one of the deleterious alleles (CYP2C9*3, *13, *14, *30, and Arg132Gln) as heterozygotes. After 3 months of losartan treatment, systolic blood pressure was not lowered in two patients with CYP2C9* 1/*30, suggesting that they exhibited impaired in vivo CYP2C9 activity. CYP2C9*30 might be associated with a diminished response to the antihypertensive effects of losartan.
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.
Summary
To elucidate predisposing factors for enlargement of intra-cerebral hematoma (ICH) during warfarin therapy, we reviewed 47 patients on warfarin who developed acute ICH and determined ...relationships among ICH enlargement, INR reversal and clinical data. Among 36 patients treated to counteract the effects of warfarin within 24 h of onset, ICH increased in 10 patients (enlarged group), but remained unchanged in the remaining 26 (unchanged group), while ICH remained unchanged in another 11 patients in whom the effect of warfarin was reversed after 24 h. The international normalized ratio (INR) was counteracted immediately in 11 patients treated with prothrombin complex concentrate (PCC) but gradually in the other 36 treated by reducing the dose of warfarin, or by administering vitamin K or fresh frozen plasma. Multivariate analysis with a logistic regression model showed an INR value <2.0 at admission or for 24 h after immediate INR correction with PCC prevented ICH enlargement (OR 0.069, 95%CI 0.006-0.789, p = 0.031). An INR value of >2.0 within 24 h of ICH seems an important predisposing factor for ICH enlargement.
White-coat hypertension (HT) and masked HT can be identified by home blood pressure (BP) measurement. The prevalence of these subtypes and the associated risk of cardiovascular disease have not been ...fully investigated among Japanese hypertensive patients. The risk of cardiovascular events due to HT and its relationship with home BP measurement were examined among Japanese hypertensive patients receiving treatment in the Japan Hypertension Evaluation with Angiotensin II Antagonist Losartan Therapy (J-HEALTH) study, a nationwide prospective observational study. Both home and clinic BP were measured during treatment, and the occurrence of cardiovascular events was monitored in 4,596 Japanese patients (mean age of 60.8 years, 43.2% men, and mean follow-up period of 3.5 years). HT was defined as a systolic BP > or =140 mmHg for clinic BP and > or =135 mmHg for home BP while on treatment. The relative risk of all cardiovascular events and stroke increased along with higher clinic and home BP levels during treatment. The prevalence of white-coat HT, masked HT, well-controlled HT, and poorly controlled HT was 12.6%, 19.5%, 23.8%, and 44.1%, respectively. The relative risk of cardiovascular events was not significantly increased in the poorly controlled HT (relative risk RR: 2.05, 95% confidence interval CI: 0.77-5.45), white-coat HT (RR: 0.77, 95% CI: 0.15-3.96), and masked HT (RR: 2.00, 95% CI: 0.67-5.98) subgroups compared with the well-controlled-HT subgroup; however, the risk of masked HT was similar to that of poorly controlled HT. Monitoring both clinic and home BP is important to diagnose masked HT and to prevent cardiovascular disease in this subtype of HT. However, further investigation is required to fully characterize the cardiovascular risks associated with masked HT among Japanese patients receiving treatment.
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