Stroke is the world’s third leading cause of death. One cause of stroke, intracranial aneurysm, affects ~2% of the population and accounts for 500,000 hemorrhagic strokes annually in midlife (median age 50), most often resulting in death or severe neurological impairment1. The pathogenesis of intracranial aneurysm is unknown, and because catastrophic hemorrhage is commonly the first sign of disease, early identification is essential. We carried out a multistage genome-wide association study (GWAS) of Finnish, Dutch and Japanese cohorts including over 2,100 intracranial aneurysm cases and 8,000 controls. Genome-wide genotyping of the European cohorts and replication studies in the Japanese cohort identified common SNPs on chromosomes 2q, 8q and 9p that show significant association with intracranial aneurysm with odds ratios 1.24-1.36. The loci on 2q and 8q are new, whereas the 9p locus was previously found to be associated with arterial diseases, including intracranial aneurysm2-5. Associated SNPs on 8q likely act via SOX17, which is required for formation and maintenance of endothelial cells6-8, suggesting a role in development and repair of the vasculature; CDKN2A at 9p may have a similar role9. These findings have implications for the pathophysiology, diagnosis and therapy of intracranial aneurysm.

Stent-assisted coil embolization is a feasible method for the endovascular treatment of wide-necked intracranial aneurysms that are difficult to treat surgically or with balloon-assisted embolization during acute SAH. The risk of subsequent rerupture of the aneurysm seems to be reduced for aneurysms treated early compared with that for nonsecured aneurysms.

In a series of 1314 consecutive patients with cerebral aneurysms from a defined catchment area in eastern Finland (870,000 inhabitants), 561 patients (43%) had middle cerebral artery aneurysms (MCAAs). One or more associated aneurysms were common; 221 patients with MCAAs (39%) had multiple intracranial aneurysms (MIA). In other words, three-fourths (73%) of all patients with MIA had at least one MCAA. Multiple MCAAs, found in 111 patients (20%), were common in this Finnish population. One hundred of these patients had bilateral MCAAs, of whom 63 had mirror aneurysms, that is, aneurysms at the same site but on different sides. Thirty-five patients had "pure" mirror aneurysms, that is, they did not have any other aneurysms. Most MCAAs (81%) were located at the bifurcation. Three-fourths (72%) of the proximal MCAAs were associated with MIA. Giant aneurysms were significantly more common as single MCAAs than as any other single aneurysm. The frequency of intracerebral hematomas (42%) was by far higher in patients with MCAAs than in patients with ruptured aneurysms at other sites. Most of the intracerebral hematomas occurred in patients with bifurcation MCAAs that pointed laterally. Patients with MCAAs had surprisingly bad management outcomes despite good surgical results in patients with good Hunt and Hess grades. There were significantly more poor outcomes (Glasgow Outcome Scale score, 3-5) among patients with ruptured MCAAs than among those with any other anterior circulation aneurysms (32 and 25%, respectively). Also, the multiplicity of aneurysms increased the risk for poor outcome, which occurred in 39% of the patients who had MIA with one MCAA and 37% of those who had multiple MCAAs. Epilepsy, severe hemiparesis, and visual field deficits were the most common disabilities in long-term survivors, associated far more frequently with MCAAs than with aneurysm at other sites.

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