Stroke; a journal of cerebral circulation
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Statistical sciences have recently made advancements that allow improved precision or reduced sample size in clinical research studies. Herein, we review 4 of the more promising: (1) improvements in approaches for dose selection trials, (2) approaches for sample size adjustment, (3) selection of study end point and associated statistical methods, and (4) frequentist versus Bayesian statistical methods. Whereas each of these holds the opportunity for more efficient trials, each are associated with the need for more stringent assumptions or increased complexity in the interpretation of results. The opportunities for these promising approaches, and their associated "costs," are reviewed.
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Brain inflammation holds promise as a therapeutic target in subacute stages of ischemic stroke. At the cellular level, postischemic inflammation is dominated by cells of the innate immune system with resident microglia/brain macrophages and blood-derived monocytes/macrophages being the most important cell types involved. ⋯ USPIO-laden macrophages cause typical signal changes in MRI of infarcted brain parenchyma, which has been demonstrated in studies of both experimental ischemia and human stroke. USPIO-enhanced MRI may therefore represent an important tool to address the role of macrophages for ischemic lesion development both in basic science and clinical studies.
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Induced hypothermia is one of the most promising neuroprotective therapies. Technological limitations and homeostatic mechanisms that maintain core body temperature have impeded the clinical use of hypothermia. Recent advances in intravascular cooling catheters and successful trials of hypothermia for cardiac arrest and neonatal asphyxia renewed interest in hypothermia for stroke, resulting in early phase clinical trials and plans for further development. This review elaborates on the clinical implications of hypothermia research in stroke and technical and logistical issues associated with the application of hypothermia.
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Comparative Study
Cardiac autonomic nervous system and risk of arrhythmias in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited systemic microangiopathy with prevalently cerebral manifestations. Among the causes of death, sudden unexpected death seems to occur in a significant number of CADASIL patients. Because potential causes of sudden unexpected death may include cardiac arrhythmias and myocardial infarction, we evaluated risk factors for life-threatening arrhythmias, such as reduced heart rate variability, sympathetic overactivity and QT interval (QTc) prolongation, in 23 CADASIL patients. The relationship of these changes with brain MRI pattern was also investigated. ⋯ We found a statistically significant reduction in all frequency domain parameters of heart rate variability associated with a higher low frequency/high frequency ratio for CADASIL patients with respect to normal subjects. These data are consistent with autonomic derangement and suggests that CADASIL patients may be at risk for life-threatening arrhythmias. This could at least in part explain their higher recurrence of sudden unexpected death and should be taken into account in planning therapy.
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Comparative Study
Spontaneous and endothelial-independent vasodilation are impaired in patients with spontaneous carotid dissection: a case-control study.
We undertook this case-control study in patients with unilateral spontaneous dissection of the cervical internal carotid artery to investigate spontaneous and endothelium-independent dilation of the nondissected, contralateral carotid arteries and the ipsilateral brachial artery using high-resolution ultrasound. ⋯ Vasodilation abnormalities may be a predisposing factor for spontaneous dissection of the cervical internal carotid artery.