Unruptured intracranial aneurysms (UIA) constitute a significant public health problem in the United States (which is growing in magnitude). The prevention of hemorrhagic stroke in patients with UIA may be possible with a better understanding of the natural history of these lesions as well as the short and long-term benefits and risks associated with their repair. The current proposal represents a continuation of the first phase of the International Study of Unruptured Intracranial Aneurysms (ISUIA). Its primary objectives are to 1) define a critical aneurysm size above which there is a significant risk of future rupture among patients with UIA and no history of subarachnoid hemorrhage (SAH); 2) compare the risk of future rupture of UIA, disability, and death among patients with and without a history of prior SAH from a different source and to determine whether or not the risk of future rupture varies directly with aneurysmal size among patients with a history of prior SAH; and 3) define the surgical and endovascular morbidity and mortality involved with repair of UIA across a broad spectrum of populations, surgeons, and interventional neuroradiologists with special reference to the size and location of the aneurysm, history of SAH from another source, and other confounding variables such as age and associated medical conditions. The current proposal involves the prospective entry and follow-up of 2400 new cases with UIA (3500 total cases were entered in Phase I), and the continued follow-up of living cases with UIA entered to date at the 53 participating centers. The primary analysis will examine neurologic outcome, specifically, fatal and non-fatal intracranial hemorrhagic stroke secondary to aneurysmal rupture. Secondary analyses will examine other aneurysmal complications such as ischemic stroke and death from all causes. The prognostic significance of several independent clinical and radiological variables with respect to stroke due to aneurysmal rupture and mortality will also be analyzed using a Cox proportional hazards model. In addition, extensive planning has been undertaken to establish a molecular genetics component to this study to identify specific genetic defects predisposing the development and rupture of intracranial aneurysms. Funding for this component will be requested via a separate proposal submitted as a supplement to the current application.
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