The most common and potentially treatable cause of secondary neurological injury in this population in patients with aneurysmal subarachnoid hemorrhage (SAH) is delayed ischemic deficit (DID). This phenomenon is fundamentally a reduction of cerebral blood flow (CBF) below critical ischemic thresholds, occurring days after the onset of hemorrhage. Two important physiological processes involved in the CBF reduction are the severe narrowing of intracranial arteries (vasospasm) and a loss of normal autoregulatory function in the distal circulation. Recent preliminary studies have shown that early administration of statins can reduce the incidence of DID and symptomatic arterial vasospasm This benefit may be due an increase in cerebral blood flow, autoregulatory responses to low flow, or non-hemodynamic mechanisms. The primary objective of this project is to investigate the effect of statin therapy on CBF in 50 patients with aneurysmal SAH who are randomized evenly to receive or not receive statins in a blinded design. We will measure and compare global CBF after SAH between the two treatment groups using Positron Emission Tomography (PET) at two time points: between 3 and 5 days after onset of SAH and again at day 7.
(Aim 1). We will compare autoregulatory function between treatment groups at days 7 (Aim 2). PET measurements of Oxygen Extraction Fraction (OEF) will also be made at baseline and 7 days and compared between groups (Aim 3). Secondary aims include the comparison between the two treatment groups of the incidence of symptomatic vasospasm, incidence of arteriographic vasospasm, and ultimate neurological outcome. More detailed analyses of hemodynamic and metabolic data will also be performed, including comparisons between treatment groups in regional CBF, OEF, Cerebral Blood Volume (CSV, measured in order to calculate OEF) and autoregulatory function for arterial territories with and without arteriographic vasospasm. We will determine if statin therapy improves CBF in patients with aneurysmal subarachnoid hemorrhage. This improvement, if present, may be due to improved basal CBF, improved autoregulatory function, or a mitigation of large arterial narrowing. The information gain from this study will help us to better understand the mechanism of action of statins. This knowledge may be useful in the design of future studies with statins and in the development of other therapies aimed at similar mechanisms.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center (P50)
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Special Emphasis Panel (ZNS1-SRB-G)
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Washington University
Saint Louis
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Goyal, Manu S; Hoff, Brian G; Williams, Jennifer et al. (2016) Streamlined Hyperacute Magnetic Resonance Imaging Protocol Identifies Tissue-Type Plasminogen Activator-Eligible Stroke Patients When Clinical Impression Is Stroke Mimic. Stroke 47:1012-7
An, Hongyu; Ford, Andria L; Eldeniz, Cihat et al. (2016) Reperfusion Beyond 6 Hours Reduces Infarct Probability in Moderately Ischemic Brain Tissue. Stroke 47:99-105
Chen, Yasheng; Dhar, Rajat; Heitsch, Laura et al. (2016) Automated quantification of cerebral edema following hemispheric infarction: Application of a machine-learning algorithm to evaluate CSF shifts on serial head CTs. Neuroimage Clin 12:673-680
Diringer, Michael N; Dhar, Rajat; Scalfani, Michael et al. (2016) Effect of High-Dose Simvastatin on Cerebral Blood Flow and Static Autoregulation in Subarachnoid Hemorrhage. Neurocrit Care 25:56-63
An, Hongyu; Ford, Andria L; Chen, Yasheng et al. (2015) Defining the ischemic penumbra using magnetic resonance oxygen metabolic index. Stroke 46:982-8
Dhar, Rajat; Diringer, Michael N (2015) Relationship between angiographic vasospasm, cerebral blood flow, and cerebral infarction after subarachnoid hemorrhage. Acta Neurochir Suppl 120:161-5
Curfman, David; Connor, Lisa Tabor; Moy, Hawnwan Philip et al. (2014) Accuracy of emergency medical services-reported last known normal times in patients suspected with acute stroke. Stroke 45:1275-9
Rubin, Michael A; Dhar, Rajat; Diringer, Michael N (2014) Racial differences in withdrawal of mechanical ventilation do not alter mortality in neurologically injured patients. J Crit Care 29:49-53
Sanelli, P C; Sykes, J B; Ford, A L et al. (2014) Imaging and treatment of patients with acute stroke: an evidence-based review. AJNR Am J Neuroradiol 35:1045-51
Vellimana, Ananth K; Yarbrough, Chester K; Blackburn, Spiros et al. (2014) Intravenous tissue-type plasminogen activator therapy is an independent risk factor for symptomatic intracerebral hemorrhage after carotid endarterectomy. Neurosurgery 74:254-61

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