MMD incidence was higher in Japan and China than in Taiwan and North America and presenting symptoms showed regional differences, which are thus far unexplained. Population based data on MMD in Europe are lacking.

BACKGROUND Intracranial aneurysm rupture prediction is poor, with only a few risk factors for rupture identified and used in clinical practice. OBJECTIVE To provide an overview of all the risk factors (including genetic, molecular, morphological, and hemodynamic factors) that have potential for use in clinical practice. METHODS We systematically searched PubMed and EMBASE and focused on factors that can be easily assessed in clinical practice, might be used for rupture prediction in clinical practice, and/or are potential targets for further research. Studies were categorized according to methodological quality, and a meta-analysis was performed, if possible. RESULTS We included 102 studies describing 144 risk factors that fulfilled predefined criteria. There was strong evidence for the morphological factors irregular shape (studied in 4 prospective cohort studies of high-quality, pooled odds ratio [OR] of 4.8 [95% confidence interval 2.7-8.7]), aspect ratio (pooled OR 10.2 [4.3-24.6]), size ratio, bottleneck factor, and height-to-width ratio to increase rupture risk. Moderate level of evidence was found for presence of contact with the perianeurysmal environment (pooled OR 3.5 [1.4-8.4]), unbalanced nature of this contact (pooled OR 17.8 [8.3-38.5]), volume-to-ostium ratio, and direction of the aneurysm dome (pooled OR 1.5 [1.2-1.9]). CONCLUSION Irregular aneurysm shape was identified as a risk factor with potential for use in clinical practice. The risk factors aspect ratio, size ratio, bottleneck factor, height-to-width ratio, contact with the perianeurysmal environment, volume-to-ostium ratio, and dome-direction should first be confirmed in multivariate analysis and incorporated in prediction models.

BACKGROUND AND PURPOSE: Previous studies have suggested that gadolinium enhancement of the wall of unruptured intracranial aneurysms on MR imaging may reflect aneurysm wall instability. However, all previous studies were cross-sectional. In this longitudinal study, we investigated whether aneurysm wall enhancement is associated with an increased risk of aneurysm instability. MATERIALS AND METHODS: We included all patients 18 years of age or older with Ն1 unruptured aneurysm from the University Medical Center Utrecht, the Netherlands, who were included in 2 previous studies with either 3T or 7T aneurysm wall MR imaging and for whom it was decided not to treat the aneurysm but to monitor it with follow-up imaging. We investigated the risk of growth or rupture during follow-up of aneurysms with and without gadolinium enhancement of the aneurysm wall at baseline and calculated the risk difference between the 2 groups with corresponding 95% confidence intervals. RESULTS: We included 57 patients with 65 unruptured intracranial aneurysms. After a median follow-up of 27 months (interquartile range, 20-31 months), growth (n ϭ 2) or rupture (n ϭ 2) was observed in 4 of 19 aneurysms (21%; 95% CI, 6%-54%) with wall enhancement and in zero of 46 aneurysms (0%; 95% CI, 0%-8%) without enhancement (risk difference, 21%; 95% CI, 3%-39%). CONCLUSIONS: Gadolinium enhancement of the aneurysm wall on MR imaging is associated with an increased risk of aneurysm instability. The absence of wall enhancement makes it unlikely that the aneurysm will grow or rupture in the short term. Larger studies are needed to investigate whether aneurysm wall enhancement is an independent predictor of aneurysm instability.

Intracranial aneurysms are common with a prevalence of 3%. 1 The availability of noninvasive imaging techniques has increased, which coincided with an increase in incidental detection of aneurysms.2 Although only a minority of aneurysms ruptures, the consequences of aneurysmal subarachnoid hemorrhage are enormous, because of the young age at which it occurs, and the high case fatality and morbidity. Preventive treatment of unruptured aneurysms carries a risk of complications.4 New treatment strategies, therefore, inhibiting the formation, growth, and rupture of aneurysms are needed. To develop such treatment strategies, we need more insight into the pathogenesis of aneurysm development and rupture. Studies investigating differences in gene expression in aneurysms versus controls and in ruptured versus unruptured aneurysms may identify genes and pathways involved in development and rupture of aneurysms. Previous studies were small and, used microarray techniques, 5-12 and extracranial instead of intracranial arteries as control. [6][7][8][9]11,12 Recent advances in Background and Purpose-Analyzing genes involved in development and rupture of intracranial aneurysms can enhance knowledge about the pathogenesis of aneurysms, and identify new treatment strategies. We compared gene expression between ruptured and unruptured aneurysms and control intracranial arteries. Methods-We determined expression levels with RNA sequencing. Applying a multivariate negative binomial model, we identified genes that were differentially expressed between 44 aneurysms and 16 control arteries, and between 22 ruptured and 21 unruptured aneurysms. The differential expression of 8 relevant and highly significant genes was validated using digital polymerase chain reaction. Pathway analysis was used to identify enriched pathways. We also analyzed genes with an extreme pattern of differential expression: only expressed in 1 condition without any expression in the other. Results-We found 229 differentially expressed genes in aneurysms versus controls and 1489 in ruptured versus unruptured aneurysms. The differential expression of all 8 genes selected for digital polymerase chain reaction validation was confirmed. Extracellular matrix pathways were enriched in aneurysms versus controls, whereas pathways involved in immune response and the lysosome pathway were enriched in ruptured versus unruptured aneurysms. Immunoglobulin genes were expressed in aneurysms, but showed no expression in controls. Conclusions-For