The Familial Intracranial Aneurysm (FIA) study protocol

BACKGROUND: Subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms (IAs) occurs in about 20,000 people per year in the U.S. annually and nearly half of the affected persons are dead within the first 30 days. Survivors of ruptured IAs are often left with substantial disability. Thus, primary prevention of aneurysm formation and rupture is of paramount importance. Prior studies indicate that genetic factors are important in the formation and rupture of IAs. The long-term goal of the Familial Intracranial Aneurysm (FIA) Study is to identify genes that underlie the development and rupture of intracranial aneurysms (IA). METHODS/DESIGN: The FIA Study includes 26 clinical centers which have extensive experience in the clinical management and imaging of intracerebral aneurysms. 475 families with affected sib pairs or with multiple affected relatives will be enrolled through retrospective and prospective screening of potential subjects with an IA. After giving informed consent, the proband or their spokesperson invites other family members to participate. Each participant is interviewed using a standardized questionnaire which covers medical history, social history and demographic information. In addition blood is drawn from each participant for DNA isolation and immortalization of lymphocytes. High- risk family members without a previously diagnosed IA undergo magnetic resonance angiography (MRA) to identify asymptomatic unruptured aneurysms. A 10 cM genome screen will be performed to identify FIA susceptibility loci. Due to the significant mortality of affected individuals, novel approaches are employed to reconstruct the genotype of critical deceased individuals. These include the intensive recruitment of the spouse and children of deceased, affected individuals. DISCUSSION: A successful, adequately-powered genetic linkage study of IA is challenging given the very high, early mortality of ruptured IA. Design features in the FIA Study that address this challenge include recruitment at a large number of highly active clinical centers, comprehensive screening and recruitment techniques, non-invasive vascular imaging of high-risk subjects, genome reconstruction of dead affected individuals using marker data from closely related family members, and inclusion of environmental covariates in the statistical analysis

Contemporary management of incidental intracranial aneurysms

The management of unruptured intracranial aneurysms has changed significantly in recent years and continues to evolve. The three main factors that have affected the management of unruptured intracranial aneurysms are as follows: 1) increased availability of noninvasive imaging technology, resulting in increased detection of incidental aneurysms; 2) improved understanding of the natural history of unruptured aneurysms; and 3) the advent of neuroendovascular therapy. In this report, the authors discuss the implications of these factors in the diagnosis and management of truly incidental, asymptomatic aneurysms and review the current practice patterns at their institution. Historical and current articles regarding noninvasive neuroimaging, aneurysm screening, endovascular and surgical therapy, and the natural history of unruptured aneurysms were reviewed. Current practices used for diagnosis and management of incidental aneurysms at the authors' institution were also reviewed. The management of incidental intracranial aneurysms has become an increasingly controversial subject in recent years. Improvements in noninvasive imaging resulting in detection of an increasing number of incidental aneurysms, the establishment of endovascular therapy as an attractive alternative to surgery, and studies indicating a more benign natural history for unruptured aneurysms than previously thought have led to significant changes in neurosurgical practice. Safety and long-term efficacy are the goals of treatment for unruptured aneurysms. Until conclusive studies are completed, the experience of the neurovascular team at each institution and the art of patient selection for treatment will continue to play a fundamental role in the management of these lesions