Low-molecular-weight heparin versus aspirin for acute ischemic stroke with large artery occlusive disease: subgroup analyses from the Fraxiparin in Stroke Study for the treatment of ischemic stroke (FISS-tris) study.

BACKGROUND AND PURPOSE: The Fraxiparin in Stroke Study for the treatment of ischemic stroke (FISS-tris) study showed no superiority of low-molecular-weight heparin (LMWH) over aspirin for the primary end point (Barthel Index) in acute ischemic stroke due to large artery occlusive disease. This study aims to evaluate the efficacy of LMWH and aspirin in selected subgroups so as to generate hypotheses for further studies. METHODS: The FISS-tris study was a multicenter, randomized trial to investigate the efficacy and safety of LMWH (nadroparin calcium 3800 antifactor Xa IU/0.4 mL subcutaneously twice daily) or aspirin (160 mg once daily) for the treatment of patients with acute ischemic stroke and large artery occlusive disease. The primary outcome was the Barthel Index score dichotomized at 85 6 months poststroke. Exploratory subgroup analysis was performed using different levels of baseline characteristics and the distribution of symptomatic arteries. RESULTS: Compared with aspirin, LMWH improved outcome among older patients >68 years (P=0.043; OR, 1.86; 95% CI, 1.02-3.41) without ongoing antiplatelet treatment on admission (P=0.029; OR, 1.85; 95% CI, 1.06-3.21) and with symptomatic posterior circulation arterial disease (P=0.001; OR, 5.76; 95% CI, 2.00-16.56). CONCLUSIONS: Our findings suggest that LMWH may be of benefit in certain subgroups of patients with acute cerebral infarct and large artery occlusive disease. Hence, further investigation of LMWH may be justified in subgroups such as the elderly, nonusers of antiplatelet agents, and patients with posterior circulation stenosis. CLINICAL TRIAL REGISTRATION: URL: www.strokecenter.org/trials. Unique identifier: registration no. 493.

Preliminary findings of external counterpulsation for ischemic stroke patient with large artery occlusive disease.

BACKGROUND AND PURPOSE: We aimed to investigate the feasibility and therapeutic effect of external counterpulsation (ECP) in ischemic stroke. METHODS: The trial was a randomized, crossover, assessment-blinded, proof-of-concept trial. ECP treatment consisted of 35 daily 1-hour sessions. Patients were randomized to either early (ECP weeks 1 to 7 and no ECP weeks 8 to 14) or late group (no ECP weeks 1 to 7 and ECP weeks 8 to 14). Primary outcomes were an overall change in National Institutes of Health Stroke Scale (NIHSS) and cerebral blood flow estimated by color velocity imaging quantification. Secondary outcomes were change in NIHSS, color velocity imaging quantification, favorable functional outcome (modified Rankin scale, 0 to 2), and stroke recurrence at weeks 7 and 14, respectively. RESULTS: Fifty patients were recruited. At week 7, there was a significant change in NIHSS (early 3.5 vs late 1.9; P=0.042). After adjusting for treatment sequence, ECP was associated with a favorable trend of change in NIHSS of 2.1 vs 1.3 for non-ECP (P=0.061). Changes of color velocity imaging quantification were not significant but tended to increase with ECP. At week 14, a favorable functional outcome was found in 100% of early group patients compared to 76% in the late group (P=0.022). CONCLUSIONS: ECP is feasible for ischemic stroke patients with larger artery disease.

Is counterpulsation a potential therapy for ischemic stroke?

BACKGROUND: Despite the rapid progress in stroke prevention, effective acute stroke treatment except for thrombolysis is still lacking. Hypoperfusion is related to unfavorable functional outcome, further strokes and long-term mortality. Therefore, the need for a safe and effective way of increasing the cerebral blood flow seems obvious. Currently, there is a growing body of evidence to suggest that external counterpulsation (ECP) may enhance the blood supply to the brain and thus may be beneficial to patients with ischemic stroke. METHODS: A MEDLINE search in combination with a search for papers in Chinese literature in the Wan Fang and China Academic Journal databases was carried out. RESULTS: Preliminary investigations suggested that ECP may improve the clinical outcome of stroke patients. However, well-designed clinical studies exploring the therapeutic effects of ECP in ischemic stroke are very limited. CONCLUSIONS: Randomized-controlled trials with a large sample size are needed to further define the efficacy and safety of ECP in acute stroke management. Future studies should provide insight into the value of ECP in ischemic stroke as well as its possible mechanisms.

Total cerebral blood flow estimated by color velocity imaging quantification ultrasound: a predictor for recurrent stroke?

Although the Virchow's triad on thrombosis includes reduced blood flow as a factor, there has been relatively little data on the importance of total cerebral blood flow on the risk of subsequent stroke. In the current study, we investigate whether total cerebral blood flow helps predict stroke recurrence. Extracranial arterial blood flow volume estimated by color velocity imaging quantification ultrasound (CVIQ) is an index of cerebral blood flow measurement. We performed a cohort study of 210 consecutive acute stroke patients. Patients were studied with transcranial Doppler and duplex ultrasound for intra- and extracranial large artery disease within 3 days of symptom onset. The association between the risk of recurrent stroke and CVIQ was analyzed with Cox proportional hazards model. Thirty-nine patients (17.7%) developed an ischemic stroke during a mean follow-up of 47.5 months. The mean extracranial blood flow volume was significantly lower for patients who had a recurrent stroke than those without (594.4+/-130.3 versus 683.8+/-176.9 mL/min; P=0.003). In a Cox proportional hazards model adjusting for potential confounding variables, extracranial blood flow volume (hazard ratio (HR) for lowest tertile, 4.1; 95% confidence interval (CI), 1.5 to 11.0) along with male sex (HR, 2.5; 95% CI, 1.3 to 5.1), diabetes (HR, 2.5; 95% CI, 1.2 to 5.0) and large artery stenosis (HR, 2.2; 95% CI, 1.1 to 4.4) were independent predictors for stroke recurrence. Our data indicated that patient with low amount of blood flow to the brain is at risk of recurrent stroke.

Comprehensive assessment for autonomic dysfunction in different phases after ischemic stroke.

BACKGROUND AND PURPOSE: Studies mostly use the analysis of heart rate variability to measure cardiovascular autonomic regulation in ischemic stroke. Besides power spectral analysis of heart rate variability, this study sought to determine whether autonomic function was impaired during different phases in ischemic stroke by Ewing's battery of autonomic function tests. METHODS: Ninety-four patients with ischemic stroke (34 patients in acute phase and 60 patients in chronic phase, average six-months after stroke onset) and thirty-seven elderly controls were recruited. Ewing's battery autonomic function tests and power spectral analysis of heart rate variability were performed in all the subjects. RESULTS: From power spectral analysis of heart rate variability, stroke patients of both acute and chronic phases had significantly lower low frequency power spectral density than controls. From Ewing's battery of autonomic function tests, patients in acute phase showed impairment in two parasympathetic tests (Valsalva ratio: P = 0·002; heart rate response to deep breathing: P < 0·001) and those in chronic phase showed impairment in all parasympathetic tests (all P < 0·05) in comparison with controls. CONCLUSIONS: The comprehensive assessment indicates that autonomic dysfunction occurs in acute phase of ischemic stroke and may persist up to six-months after stroke. Parasympathetic dysfunction rather than sympathetic dysfunction is predominant after ischemic stroke.

Low-molecular-weight heparin and early neurologic deterioration in acute stroke caused by large artery occlusive disease.

BACKGROUND: Patients with acute ischemic stroke and large artery occlusive disease (LAOD) have an increased risk for early neurologic deterioration (END) due to progressive stroke, early recurrent ischemic stroke(ERIS), or symptomatic intracranial cerebral hemorrhage(SICH). Low-molecular-weight heparin (LMWH)has been widely advocated to prevent venous thromboembolism,but its risks and benefits in early ischemic stroke are inadequately defined. OBJECTIVE: To determine the efficacy and safety of LMWH in treating END in patients with acute ischemic stroke and LAOD. DESIGN: Post hoc analysis of randomized, controlled trial. SETTING: Academic research. PATIENTS: Among 603 patients recruited, 353 patients(180 treated with LMWH, 173 with aspirin) had acute ischemic stroke and LAOD. INTERVENTIONS: Patients were randomly assigned to receive either subcutaneous LMWH or oral aspirin within 48 hours after stroke onset for 10 days, then all received aspirin once daily for 6 months. MAIN OUTCOME MEASURES: We assessed whether LMWH was superior to aspirin for the prevention of END within the first 10 days after index stroke. Early neurologic deterioration was defined as a composite end point of progressive stroke, ERIS, and SICH. RESULTS: Among 353 patients included in the study, END within the first 10 days occurred in 6.7% of LMWH allocated patients (12 of 180 patients) compared with 13.9% of aspirin-allocated patients (24 of 173). Low molecular-weight heparin was significantly associated with the reduction of END(absolute risk reduction, 7.2%; odds ratio [OR], 0.44; 95% CI, 0.21-0.92). When individual components of END were examined, LMWH was significantly associated with a lower frequency of stroke progression within the first 10 days compared with aspirin(5.0% [9 of 180] vs 12.7% [22 of 173]; OR, 0.36; 95%CI, 0.16-0.81). Meanwhile, among those taking LMWH vs aspirin, the frequency rates of ERIS were 1.1% (2 of 180) vs 0 (0); 0.6% (1 of 180) vs 1.2% (2 of 173) for SICH;and 2.2% (4 of 180) vs 2.9% (5 of 173) for symptomatic and asymptomatic cerebral hemorrhage, respectively; they showed nonsignificant trends. Early neurologic deterioration was significantly associated with 6-month disability with both LMWH(OR, 12.75; 95% CI, 3.27-49.79 on Barthel Index and OR, 18.15; 95% CI, 2.09-157.93 on modified Rankin Scale) and aspirin (OR, 6.09; 95% CI,2.44-15.20 on Barthel Index and OR, 7.50; 95% CI, 2.08-27.04 on modified Rankin Scale) groups. CONCLUSIONS: For patients with acute ischemic stroke and LAOD, treatment with LMWH within 48 hours of stroke may reduce END during the first 10 days, mainly by preventing stroke progression. The similar rate of cerebral hemorrhage between LMWH and aspirin demonstrated that LMWH may be safely used in acute ischemic stroke. TRIAL REGISTRATION: stroke center.org/trials Identifier: FISS -tris

Preliminary findings of the effects of autonomic dysfunction on functional outcome after acute ischemic stroke.

BACKGROUND AND PURPOSE: Impaired autonomic function is common in the acute poststroke phase but little is known about its effects on functional outcome after acute ischemic stroke. This study sought to investigate the impact of autonomic dysfunction by Ewing's classification on functional outcome 2 months after acute ischemic stroke. METHODS: 34 consecutive acute ischemic stroke patients within 7 days after onset were enrolled. On admission, autonomic function was assessed by Ewing's battery tests. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS), autonomy in activities of daily living by the Barthel Index (BI), and global disability by the modified Rankin Scale (mRS). BI and mRS were also evaluated 2 months after ischemic stroke onset. RESULTS: On admission, eight patients were diagnosed as minor autonomic dysfunction and 26 patients as relatively severe autonomic dysfunction. The prevalence of relatively severe autonomic dysfunction in ischemic stroke patients was 76.5%. There were no significant differences in baseline characteristics between the minor and severe autonomic dysfunction groups. 2 months after stroke onset, the mean BI score of patients with minor autonomic dysfunction and severe autonomic dysfunction increased from 76.3±15.3 on admission to 95.0±7.1, 66.5±15.2 on admission to 74.8±15.9 respectively. The mean BI score after 2-month stroke onset and the change in BI from admission to 2-month outcome (delta BI) in patients with severe autonomic dysfunction were lower than those in patients with minor autonomic dysfunction (all P<0.05). CONCLUSIONS: Autonomic dysfunction occurs in acute stroke patients. Relatively severe autonomic dysfunction is related to an unfavorable functional outcome in patients with acute ischemic stroke.

Plasma level of sICAM-1 is associated with the extent of white matter lesion among asymptomatic elderly subjects.

OBJECTIVE: Inflammatory endothelial activation mediated by intercellular adhesion molecule-1 (ICAM-1) plays a role in the pathogenesis of large- and small-vessel disease. We explored the association between soluble ICAM-1 (sICAM-1) and white matter lesion (WML) as a manifestation of cerebral small-vessel disease. METHODS: One hundred and seventy-five elderly individuals aged >or= 60 without neurological deficits were studied. Subcortical deep white matter hyperintensity (SDWMH) and periventricular hyperintensity (PVH) were rated separately. Lesions in each category were then divided into three groups (grade 0-I, grade II, grade III) according to the Fazekas scale. RESULTS: Plasma sICAM-1 levels were positively associated with grades of WML (for SDWMH: 297.4+/-135.6ng/mL in grade 0-I, 391.3+/-145.5ng/mL in grade II, and 450.2+/-232.9ng/mL in grade III, p<0.001; for PVH: 282.5+/-116.5ng/mL in grade 0-I, 402.3+/-160.4ng/mL in grade II, and 428.1+/-227.7ng/mL in grade III, p<0.001). Multivariate analysis showed higher sICAM-1 levels, age and hypertension were the independent risk factors associated with the presence and severity of WML. More than 4-fold increased risk of WML was observed in patients with the highest quartile of sICAM-1 (all WML OR=4.694, 95% CI: 1.805-12.204; moderate WML OR=4.618, 95% CI: 1.543-13.825; severe WML OR=4.893, 95% CI: 1.236-19.368). CONCLUSION: Increased plasma sICAM-1 suggests inflammatory process may be involved in the pathogenesis of WML.