Benjamin R. Kummer, MD

Backes D, Rinkel GJE,  Laban KG, Algra A, and Vergouwen MDI. Patient- and Aneurysm-Specific Risk Factors for Intracranial Aneurysm Growth: A Systematic Review and Meta-Analysis. Stroke. 2016

Three percent of the general population harbors an unruptured intracranial aneurysm (UIA). Due to their unfavorable interventional risk-benefit profile, small, asymptomatic UIAs are often left untreated and followed with serial imaging for growth—a well-established risk factor for aneurysm rupture. Because many factors associated with aneurysm growth are also associated with rupture, patients needing increased frequency of monitoring or even intervention might be identifiable by characteristics associated with aneurysm growth. Building on their previous work on aneurysm growth published in 2015 in Stroke, Baackes and colleagues further the aim of identifying patients at increased risk for rupture in this systemic review and meta-analysis of the clinical and aneurysm-specific factors associated with the growth of UIAs.

Approximately 4,000 patients and 5,000 unruptured intracranial aneurysms were studied, drawn from 18 separate publications and 15 unique patient cohorts (5 separate studies overlapped on 2 independent cohorts), followed over a mean of 2.8 years. The analysis only pooled studies that had clear definitions and effect estimates of aneurysm growth; however, a significant amount of epidemiologic and methodologic heterogeneity was present. Prospective and retrospective designs, studies with different population sizes, growth definitions, imaging modalities (CTA, DSA, MRA), Newcastle-Ottawa publication bias scores (mean 6, SD 1.9), as well as the numbers of growing UIAs were all analyzed together. Sensitivity analyses were performed to account for some, but not all of this heterogeneity. 

As previously shown, many factors associated with aneurysm rupture, like female sex, smoking, hypertension, larger aneurysm size, posterior circulation location and aneurysm shape, were also associated with aneurysm growth. However, the degree of heterogeneity in the effect estimates was moderate to substantial. The presence of multiple UIAs, which has not been readily identified as a factor associated with aneurysmal rupture, was shown to be significantly associated with aneurysm growth, raising the possibility that patients with multiple aneurysms might have a possibly connective-tissue based predilection towards more rapid growth than patients with single aneurysms, although it is important to note that this signal was also confounded by quite heterogeneous effect estimates. In contrast to their well-established association with aneurysmal rupture, family history of SAH and previous SAH were not significant factors for aneurysmal growth. Interestingly, UIA cohorts from Japan (where rates of aneurysmal rupture are higher than in European and North American cohorts) were had a lower risk of aneurysmal growth than North American cohorts. After stratifying effect estimates by study design and quality, the overall relative risk of aneurysm growth was lower in higher quality and prospective study designs than in lower-quality and retrospective designs, again suggesting that bias may have also contributed to the overall results.  

Despite the degree of heterogeneity, which the authors attempted to incompletely adjust for with sensitivity analyses, this meta-analysis suggests that aneurysmal growth and rupture may share a common pathophysiology, and yields some interesting hypothesis-generating findings on UIA growth and rupture.